Challenges and Approaches to Conducting and Interpreting the Amphibian Metamorphosis Assay and the Fish Short‐Term Reproduction Assay

Coady, Katherine K.; Lehman, Christine M.; Currie, Rebecca J.; Marino, Troy A.

doi:10.1002/bdrb.21081

Cited by 30 publications

(25 citation statements)

References 37 publications

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“…Adrenals and interrenals play a critical role during development but are also active in metabolism and, therefore, present a particularly effective target for assessing effects of EASs. Coady et al () suggest various additional tissue sampling procedures to maximize the mechanistic information that would be available for assessment following the conduct of an FSTRA or an AMA. For example, liver and kidney tissue could be preserved for potential histopathological investigations to assess whether adverse effects are due to systemic toxicity.…”

Section: Interpretation Of Results From Endocrine Screening and Testingmentioning

confidence: 99%

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

Coady

Biever

Denslow

et al. 2017

Integr Environ Assess Manag

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In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high‐throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. Integr Environ Assess Manag 2017;13:302–316. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

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Section: Interpretation Of Results From Endocrine Screening and Testingmentioning

confidence: 99%

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

Coady

Biever

Denslow

et al. 2017

Integr Environ Assess Manag

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“…This process, which can be visually observed, is one fundamental reason for using metamorphosing tadpoles for studying thyroid disruption. Based on results from us and other authors (Carlsson & Norrgren, ; Coady, Lehman, Currie, & Marino, ; Dang, ), the HLL and the developmental stage can be considered as two TH‐dependent responses in amphibian tadpoles. On the other hand, BW and SVL or SBL represent general growth and seem to be independent of TH.…”

Section: Discussionmentioning

confidence: 95%

Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles

Carlsson

Pohl

Athanassiadis

et al. 2019

J of Applied Toxicology

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Indoor dust contains a multitude of industrial chemicals, and ingestion of dust is considered an important exposure route to organic contaminants. Some of these contaminants have been shown to interfere with the thyroid system, which may result in significant consequences on public health. The amphibian metamorphosis is a thyroid hormone-dependent process, which can be used as an in vivo model for studies on thyroid hormone-disrupting potency. Three contaminants of indoor dust were tested on metamorphosing Silurana (Xenopus) tropicalis tadpoles. The tested chemicals were Tris (1,3-dichloroisopropyl) phosphate (TDCiPP), tetrabromobisphenol-A (TBBPA) and propylparaben (PrP). Measurements reflecting general growth, development progress and thyroid epithelial cell height were performed on the exposed tadpoles as well as chemical analyses of the exposure water. It was shown that TDCiPP acts as a thyroid hormone-disrupting chemical in metamorphosing tadpoles by causing increased epithelial cell height in thyroid glands after exposure to a nominal concentration of 0.010 mg/L and in higher concentrations. TBBPA caused reductions in general growth of tadpoles at the nominal concentration 0.125 mg/L, and PrP caused acute toxicity at the nominal concentration 12.5 mg/L. However, no evident indications of specific thyroid-disrupting effects caused by TBBPA or PrP were observed.

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“…Yet, differences in background EDC exposures may occur even when experimenters think they are following the guidance of this working group. Other groups have highlighted differences in endocrine endpoints in historical controls from different testing facilities used to evaluate chemicals for endocrine disrupting activities [55, 56], suggesting that this issue may be more widespread than the single commercial laboratory we examined. Our results suggest that ‘control’ animals may not be unexposed; thus, using historical controls which might have one set of background EDC exposures to compare to experimental animals with an entirely different environmental history should not be acceptable practice [11].…”

Section: Discussionmentioning

confidence: 99%

The mouse mammary gland as a sentinel organ: distinguishing ‘control’ populations with diverse environmental histories

2017

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BackgroundThere are numerous examples of laboratory animals that were inadvertently exposed to endocrine disrupting chemicals (EDCs) during the process of conducting experiments. Controlling contaminations in the laboratory is challenging, especially when their source is unknown. Unfortunately, EDC contaminations can interfere with the interpretation of data during toxicological evaluations. We propose that the male CD-1 mouse mammary gland is a sensitive bioassay to evaluate the inadvertent contamination of animal colonies.MethodsWe evaluated mammary glands collected from two CD-1 mouse populations with distinct environmental histories. Population 1 was born and raised in a commercial laboratory with unknown EDC exposures; Population 2 was the second generation raised in an animal facility with limited exposures to xenoestrogens from caging, feed, etc. Mammary glands were collected from all animals and evaluated using morphometric techniques to quantify morphological characteristics of the mammary gland.ResultsPopulation 1 (with suspected history of environmental chemical exposure) and Population 2 (with known limited history of xenoestrogen exposure) were morphologically distinguishable in adult males, prepubertal females, and pubertal females. Mammary glands from males raised in the commercial animal facility were significantly more developed, with larger ductal trees and more branching points. The appearance of these mammary glands was consistent with prior reports of male mice exposed to low doses of bisphenol A (BPA) during early development. In females, the two populations were morphologically distinct at both prepuberty and puberty, with the most striking differences observed in the number, size, and density of terminal end buds, e.g. highly proliferative structures found in the developing mammary gland.ConclusionsCollectively, these results suggest that the mouse mammary gland has the potential to be used as a sentinel organ to evaluate and distinguish animal colonies raised in different environmental conditions including potential EDC exposures. Our findings could help researchers that wish to perform a posteriori evaluations to determine whether inadvertent contamination with xenoestrogens (and potentially other EDCs) has occurred in their animal colonies, especially after new materials (feed, caging, water bottles) have been introduced. Finally, our results challenge the relatively common practice of using historical controls in toxicological experiments.

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Challenges and Approaches to Conducting and Interpreting the Amphibian Metamorphosis Assay and the Fish Short‐Term Reproduction Assay

Cited by 30 publications

References 37 publications

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles

The mouse mammary gland as a sentinel organ: distinguishing ‘control’ populations with diverse environmental histories

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