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@article{1858780,
author = {Alcaraz, Alper James G. and Baraniuk, Shaina and Mikulášek, Kamil and Park, Bradley and Lane, Taylor and Burbridge, Connor and Ewald, Jessica and Potěšil, David and Xia, Jianguo and Zdráhal, Zbyněk and Schneider, David and Crump, Doug and Basu, Niladri and Hogan, Natacha and Brinkmann, Markus and Hecker, Markus},
article_location = {ENGLAND},
article_number = {FEB},
doi = {http://dx.doi.org/10.1016/j.envpol.2021.118667},
keywords = {Benchmark dose (BMD); Selective serotonin reuptake inhibitor (SSRI); Hazard assessment; Live-animal alternatives; New approach methodology (NAM)},
language = {eng},
issn = {0269-7491},
journal = {ENVIRONMENTAL POLLUTION},
title = {Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine},
url = {http://www.sciencedirect.com/science/article/pii/S0269749121022491},
volume = {295},
year = {2022}
}
TY - JOUR
ID - 1858780
AU - Alcaraz, Alper James G. - Baraniuk, Shaina - Mikulášek, Kamil - Park, Bradley - Lane, Taylor - Burbridge, Connor - Ewald, Jessica - Potěšil, David - Xia, Jianguo - Zdráhal, Zbyněk - Schneider, David - Crump, Doug - Basu, Niladri - Hogan, Natacha - Brinkmann, Markus - Hecker, Markus
PY - 2022
TI - Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine
JF - ENVIRONMENTAL POLLUTION
VL - 295
IS - FEB
SP - "118667"
EP - "118667"
PB - ELSEVIER SCI LTD
SN - 02697491
KW - Benchmark dose (BMD)
KW - Selective serotonin reuptake inhibitor (SSRI)
KW - Hazard assessment
KW - Live-animal alternatives
KW - New approach methodology (NAM)
UR - http://www.sciencedirect.com/science/article/pii/S0269749121022491
N2 - Current approaches in chemical hazard assessment face significant challenges because they rely on live animal testing, which is time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored a molecular benchmark dose (BMD) approach using a 7-day embryo-larval fathead minnow (FHM) assay to derive transcriptomic points-of-departure (tPODs) to predict apical BMDs of fluoxetine (FLX), a highly prescribed and potent selective serotonin reuptake inhibitor frequently detected in surface waters. Fertilized FHM embryos were exposed to graded concentrations of FLX (confirmed at < LOD, 0.19, 0.74, 3.38, 10.2, 47.5 mu g/L) for 32 days. Subsets of fish were subjected to omics and locomotor analyses at 7 days post-fertilization (dpf) and to histological and biometric measurements at 32 dpf. Enrichment analyses of transcriptomics and proteomics data revealed significant perturbations in gene sets associated with serotonergic and axonal functions. BMD analysis resulted in tPOD values of 0.56 mu g/L (median of the 20 most sensitive gene-level BMDs), 5.0 mu g/L (tenth percentile of all gene-level BMDs), 7.51 mu g/L (mode of the first peak of all gene-level BMDs), and 5.66 mu g/L (pathway-level BMD). These tPODs were protective of locomotor and reduced body weight effects (LOEC of 10.2 mu g/L) observed in this study and were reflective of chronic apical BMDs of FLX reported in the literature. Furthermore, the distribution of gene-level BMDs followed a bimodal pattern, revealing disruption of sensitive neurotoxic pathways at low concentrations and metabolic pathway perturbations at higher concentrations. This is one of the first studies to derive protective tPODs for FLX using a short-term embryo assay at a life stage not considered to be a live animal under current legislations.
ER -
ALCARAZ, Alper James G., Shaina BARANIUK, Kamil MIKULÁŠEK, Bradley PARK, Taylor LANE, Connor BURBRIDGE, Jessica EWALD, David POTĚŠIL, Jianguo XIA, Zbyněk ZDRÁHAL, David SCHNEIDER, Doug CRUMP, Niladri BASU, Natacha HOGAN, Markus BRINKMANN a Markus HECKER. Comparative analysis of transcriptomic points-of-departure (tPODs) and apical responses in embryo-larval fathead minnows exposed to fluoxetine. \textit{ENVIRONMENTAL POLLUTION}. ENGLAND: ELSEVIER SCI LTD, 2022, roč.~295, FEB, s.~''118667'', 12 s. ISSN~0269-7491. Dostupné z: https://dx.doi.org/10.1016/j.envpol.2021.118667.
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