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@article{1824639,
author = {Alcaraz, Alper James G. and Mikulášek, Kamil and Potěšil, David and Park, Bradley and Shekh, Karman and Ewald, Jessica and Burbridge, Connor and Zdráhal, Zbyněk and Schneider, David and Xia, Jianguo and Crump, Doug and Basu, Nilardi and Hecker, Markus},
article_number = {15},
doi = {http://dx.doi.org/10.1021/acs.est.1c02401},
keywords = {estrogen; risk assessment; transcriptomic benchmark dose (geneBMD); endocrine disruption; alternative toxicity testing},
language = {eng},
issn = {0013-936X},
journal = {Environmental Science and Technology},
title = {Assessing the Toxicity of 17 alpha-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay},
url = {https://pubs.acs.org/doi/10.1021/acs.est.1c02401},
volume = {55},
year = {2021}
}
TY - JOUR
ID - 1824639
AU - 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
PY - 2021
TI - Assessing the Toxicity of 17 alpha-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay
JF - Environmental Science and Technology
VL - 55
IS - 15
SP - 10608-10618
EP - 10608-10618
PB - American Chemical Society
SN - 0013936X
KW - estrogen
KW - risk assessment
KW - transcriptomic benchmark dose (geneBMD)
KW - endocrine disruption
KW - alternative toxicity testing
UR - https://pubs.acs.org/doi/10.1021/acs.est.1c02401
N2 - 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; 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.
ER -
ALCARAZ, Alper James G., Kamil MIKULÁŠEK, David POTĚŠIL, Bradley PARK, Karman SHEKH, Jessica EWALD, Connor BURBRIDGE, Zbyněk ZDRÁHAL, David SCHNEIDER, Jianguo XIA, Doug CRUMP, Nilardi BASU and Markus HECKER. Assessing the Toxicity of 17 alpha-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay. \textit{Environmental Science and Technology}. American Chemical Society, vol.~55, No~15, p.~10608-10618. ISSN~0013-936X. doi:10.1021/acs.est.1c02401. 2021.
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