Dataset Information

Transcriptomic points-of-departure (tPOD) derived from a 4-day rainbow trout embryo toxicity test were protective of apical effects for 17α-ethinylestradiol

ABSTRACT: There is an urgent demand for more efficient and ethical approaches in chemical risk assessment. Using 17α-ethinylestradiol (EE2) as a model compound, this study established a live-animal alternative embryo benchmark-dose (BMD) assay for rainbow trout (RBT; Oncorhynchus mykiss) to derive transcriptomic points-of-departure (tPODs). Embryos were exposed to graded concentrations of EE2 (0, 1.13, 1.57, 6.22, 16.3, 55.1, and 169 ng/L) from hatch to 4 and up to 60 days post-hatch (dph) to assess molecular and apical responses, respectively. Whole proteome analyses of alevins did not show clear estrogenic effects, while transcriptomics revealed responses that were in agreement with apical effects including excessive accumulation of intravascular and hepatic proteinaceous fluid and significant increases in mortality at 55.1 and 169 ng/L EE2 at later time points. Transcriptomic BMD analysis estimated the median of the 20th lowest geneBMD to be 0.18 ng/L; the most sensitive tPOD. Other estimates (0.78, 3.64, and 1.63 ng/L for the tenth percentile geneBMD, first peak geneBMD distribution, and median geneBMD of the most sensitive overrepresented pathway, respectively) were within the same order of magnitude as empirically derived apical PODs for EE2 in the literature. This 4-day alternative RBT embryonic assay was effective in deriving protective tPODs for EE2.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Oncorhynchus Mykiss (rainbow Trout) (salmo Gairdneri)

TISSUE(S): Whole Body

SUBMITTER: Alper James Alcaraz

LAB HEAD: Markus Hecker

PROVIDER: PXD025251 | Pride | 2021-08-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20201116_rbtelsee2_proteinGroups_processed_1IntensityVa.csv	Csv
	3564_QEx1_Alcaraz_RBT_DMSO_A_1.raw	Raw
	3564_QEx1_Alcaraz_RBT_DMSO_B_1.raw	Raw
	3564_QEx1_Alcaraz_RBT_DMSO_C_1.raw	Raw
	3564_QEx1_Alcaraz_RBT_EE2_100A_1.raw	Raw

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Publications

Assessing the Toxicity of 17α-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay.

Alcaraz Alper James G AJG Mikulášek Kamil K Potěšil David D Park Bradley B Shekh Kamran K Ewald Jessica J Burbridge Connor C Zdráhal Zbyněk Z Schneider David D Xia Jianguo J Crump Doug D Basu Niladri N Hecker Markus M

Environmental science & technology 20210722 15

There is an urgent demand for more efficient and ethical approaches in ecological risk assessment. Using 17α-ethinylestradiol (EE2) as a model compound, this study established an embryo benchmark dose (BMD) assay for rainbow trout (RBT; <i>Oncorhynchus mykiss</i>) to derive transcriptomic points-of-departure (tPODs) as an alternative to live-animal tests. Embryos were exposed to graded concentrations of EE2 (measured: 0, 1.13, 1.57, 6.22, 16.3, 55.1, and 169 ng/L) from hatch to 4 and up to 60 da ...[more]

PMID: 34292719

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