An Amphibian Metamorphosis Assay Dietary Restriction Study: Lessons for Data Interpretation

Marini, Joseph P; Wolf, Jeffrey C.; Mingo, Valentin; Sayers, Lee E; Jamieson, Stephanie Y; Wheeler, James R.

doi:10.1002/etc.5596

Cited by 5 publications

(4 citation statements)

References 30 publications

(32 reference statements)

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“…The influence of diet type, dietary regime, and dietary quality on standardized developmental toxicity studies using amphibians, such as the AMA and LAGDA, was evaluated recently by Fort et al (2022) and Marini et al (2023). Fort et al (2022) (Leloup & Buscagalia, 1977;Shi, 2000), which is generally consistent with the findings of the present study.…”

Section: Histopathologysupporting

confidence: 89%

“…The influence of diet type, dietary regime, and dietary quality on standardized developmental toxicity studies using amphibians, such as the AMA and LAGDA, was evaluated recently by Fort et al (2022) and Marini et al (2023). Fort et al (2022) found developmental delay, as determined by a decreasing trend in stage distribution or median developmental stage at the conclusion of exposure in an AMA study in which larvae were fed ground, liquified frog brittle (FB) (Nasco, Fort Atkinson, WI, USA) regardless of additional iodide supplementation (0.06–0.6 μg/l I − ).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, in the context of the present study, none of the studies discussed above should be directly compared to the present study. Marini et al (2023) conducted an AMA study using five different feeding rations of SMN equivalent to 50% to 5% of the recommended feeding rate (OECD, 2009). Survival or clinical signs of toxicity were not observed; however, a relationship between feed ration and other traditional AMA endpoints was observed including reduced development stage; increased thyroid atrophy, decreased prevalence of thyroid follicular cell hyperplasia and hypertrophy, liver atrophy, and reduced liver vacuolation (site of glycogen storage) which is generally consistent with the dietary insufficiency findings of Fort et al (1999Fort et al ( , 2000.…”

Section: Histopathologymentioning

confidence: 99%

“…Alternatively, the pattern of delayed development and increased growth in the solvent-treated diets also suggests that alteration, most likely antagonism, of the hypothalamic-pituitary thyroid (HPT) axis may also be involved (Fort et al, 2008). Most importantly, in the context of Marini et al (2023), results from the present study suggested that the amount of diet received during feeding within reason may not be as important in inducing adverse effects as the quality of the diet as suggested by Fort et al (2023) which was seemingly affected by acetone treatment in the present study.…”

Section: Histopathologymentioning

confidence: 99%

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Inefficacy of dietary test substance administration in Amphibian Metamorphosis Assay (AMA) studies

Fort,

Wolf,

Langsch

et al. 2023

J of Applied Toxicology

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Traditionally, the Amphibian Metamorphosis Assay (AMA; OECD TG 231) is performed by exposing Xenopus laevis tadpoles to test substances dissolved in laboratory water. Recently, the use of dietary administration has been proposed to combat poorly soluble test substances in ecotoxicologically‐based regulatory endocrine disruption (ED) studies, specifically the AMA warranting an investigation into the efficacy of dietary administration. An efficacy study comprised of two phases: 1) evaluation of the physical influence of the loading process via solvent and 10, 1, and 0.1 mg/l test substance or surrogate (sunflower oil, SFO) on the Sera® Micron Nature (SMN) diet, and 2) performance of a modified AMA in which Nieuwkoop and Faber (NF) stage 51 X. laevis larvae were exposed to dechlorinated tap water using one concentration of the SFO in the diet for 21 days, was performed. In phase 1, the addition of acetone or acetone with bis(2‐propylheptyl) phthalate (DPHP) or SFO to SMN with subsequent solvent purge altered the diet reducing the density of the liquified diet and dietary pellet size following centrifugation indicative of alteration of the physical properties of the diet. Treatments used in the modified AMA were acetone alone and 0.1 mg/l SFO dissolved in acetone. These treatments were evaluated against an SMN benchmark using standard AMA endpoints. Both the acetone‐treated SMN and 0.1 mg/l SFO‐treated diets significantly reduced survival rates, 67 and 70% relative to the SMN benchmark (100%), decreased developmental stage distribution and snout‐vent length‐normalized hind limb length relative to the SMN benchmark, and slightly increased the prevalence and severity of thyroid follicular cell hypertrophy. Although the acetone‐treated diets may have impacted the hypothalamo‐pituitary‐thyroid axis, clinical signs of gastrointestinal impaction and tail flexure were also observed in the acetone‐treated diets, but not the SMN diet alone. Ultimately, test substance exposure via the diet in an AMA study can produce results that may confound data interpretation, which suggests that the traditional aqueous exposure route is generally more appropriate.

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“…The influence of diet type, dietary regime, and dietary quality on standardized developmental toxicity studies using amphibians, such as the AMA and LAGDA, was evaluated recently by Fort et al (2022) and Marini et al (2023). Fort et al (2022) (Leloup & Buscagalia, 1977;Shi, 2000), which is generally consistent with the findings of the present study.…”

Section: Histopathologysupporting

confidence: 89%

“…The influence of diet type, dietary regime, and dietary quality on standardized developmental toxicity studies using amphibians, such as the AMA and LAGDA, was evaluated recently by Fort et al (2022) and Marini et al (2023). Fort et al (2022) found developmental delay, as determined by a decreasing trend in stage distribution or median developmental stage at the conclusion of exposure in an AMA study in which larvae were fed ground, liquified frog brittle (FB) (Nasco, Fort Atkinson, WI, USA) regardless of additional iodide supplementation (0.06–0.6 μg/l I − ).…”

Section: Discussionmentioning

confidence: 99%