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


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ALCARAZ Alper James G. MIKULÁŠEK Kamil POTĚŠIL David PARK Bradley SHEKH Karman EWALD Jessica BURBRIDGE Connor ZDRÁHAL Zbyněk SCHNEIDER David XIA Jianguo CRUMP Doug BASU Nilardi HECKER Markus

Year of publication 2021
Type Article in Periodical
Magazine / Source Environmental Science and Technology
MU Faculty or unit

Central European Institute of Technology

Web fulltext
Keywords estrogen; risk assessment; transcriptomic benchmark dose (geneBMD); endocrine disruption; alternative toxicity testing
Description There is an urgent demand for more efficient and ethical approaches in ecological risk assessment. Using 17?-ethinylestradiol (EE2) as a model compound, this study established an embryo benchmark dose (BMD) assay for rainbow trout (RBT; Oncorhynchus mykiss) 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 days post-hatch (dph) to assess molecular and apical responses, respectively. Whole proteome analyses of alevins did not show clear estrogenic effects. In contrast, 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 10th percentile geneBMD, first peak geneBMD distribution, and median geneBMD of the most sensitive over-represented 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 tPODs that are protective of chronic effects of EE2.
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