Transcriptomics Points-of-Departure (tPODs) to Support Hazard Assessment of Benzo[a]pyrene in Early-Life-Stage Rainbow Trout

Environmental Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

New approach methods (NAMs) are urgently needed to address the significant ethical and economic concerns associated with live animal testing as well low throughput current toxicity frameworks. NAMs such rapid mechanistic early-life-stage fish assays promising alternatives hazard assessment approaches, they can be used derive thresholds guide decision-makers on identifying or prioritizing chemicals of concern. This study aimed benchmark concentrations from RNaseq data (transcriptomic points-of-departure; tPOD) a short-term exposure early life stages rainbow trout (RBT; Oncorhynchus mykiss) using benzo[a]pyrene (B[a]P) model compound. tPODs were then calibrated higher organizational-level responses observed during an extended 28 day period. RBT exposed 1 days post-hatch (dph) 0.079, 0.35, 1.5, 7.4, 29 μg/L (28 d time weighted average measured) B[a]P, 0.05% dimethyl sulfoxide water only controls. Benchmark concentration analysis transcriptomic at 4 dph, based most sensitive features, yielded between 0.028 0.47 B[a]P. At Cyp1a1 exhibited significantly increased catalytic activity, biochemical POD, bPODEROD,28dph 0.599 while morphometric showed growth inhibition in terms length, apical aPODlength,28dph 1.77 notable decreasing trend body weight. A pathway constructed genes end points exhibiting concentration-dependent provided further evidence supporting utility assay support chemical risk prioritization.

Язык: Английский

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Are changes in vitellogenin concentrations in fish reliable indicators of chemical-induced endocrine activity?

Ecotoxicology and Environmental Safety, Год журнала: 2023, Номер 266, С. 115563 - 115563

Опубликована: Окт. 11, 2023

Vitellogenin (VTG), a biomarker for endocrine activity, is mechanistic component of the regulatory assessment potential endocrine-disrupting properties chemicals. This review VTG data based on changes reported 106 substances in standard fish species. High intra-study and inter-laboratory variability concentrations was confirmed, as well discrepancies interpretation results large differences between dilution water versus solvent control, or due to presence outlier measurements. responses were ranked against predictions estrogen receptor agonist activity aromatase inhibition from bioactivity model output ToxCast vitro assay results, respectively. These mechanisms explained most absence systemic toxicity, magnitude response being proportional potency. Interpretation sometimes confounded by an alternative mechanism action. There evidence both false positive negative synthesis, but overall, it rare without cause concentration-dependent toxicity. To increase confidence we recommend improvements measurement methodologies greater transparency reporting (including quality control criteria performance). supports application New Approach Methodologies (NAMs) demonstrating that mammalian cell lines predictive vivo fish, suggesting could be used more broadly decision-making help reduce animal testing.

Язык: Английский

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In Silico Models for the Screening of Human Transthyretin Disruptors

Journal of Hazardous Materials, Год журнала: 2024, Номер 480, С. 136188 - 136188

Опубликована: Окт. 16, 2024

Язык: Английский

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Resource and animal use implications of the proposed REACH information requirements for endocrine disruptor assessment

Regulatory Toxicology and Pharmacology, Год журнала: 2024, Номер 151, С. 105671 - 105671

Опубликована: Июль 3, 2024

Revised information requirements for endocrine disruptor (ED) assessment of chemicals under the European Union's Registration, Evaluation, Authorisation and Restriction Chemicals (REACH) Regulation have been proposed. Implementation will substantially increase demands new data to inform ED assessment. This article evaluates potential animal use financial resource associated with two proposed policy options, highlights areas where further clarification is warranted. evaluation demonstrates that studies potentially conducted meet could tens millions animals, approach unlikely be feasible in practice. Given challenges implementing either option need minimise reliance on testing, consideration needed several aspects prior implementation requirements. includes how testing prioritised a proportionate approach; harness methodologies waive higher-tier testing; provision clear guidance particularly applying weight-of-evidence approaches. There now opportunity Commission lead way developing robust transparent process industrial which fully implements replacement, refinement, reduction animals (the 3Rs).

Язык: Английский

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Assessing plasmatic transport inhibitors of thyroid hormone in mammals in the Xenopus Eleutheroembryonic Thyroid Assay (XETA)

Environmental Science and Pollution Research, Год журнала: 2024, Номер 31(54), С. 63360 - 63373

Опубликована: Ноя. 1, 2024

Язык: Английский

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