PUBLICATION

Morbidity and mortality in Danio rerio and Pimephales promelas exposed to antilipidemic drug mixtures (fibrates and statins) during embryogenesis: Comprehensive assessment via ante and post mortem endpoints

Authors
Kingcade, A., Ahuja, N., Jefferson, A., Schaffer, P.A., Ryschon, H., Cadmus, P., Garrity, D., Ramsdell, H.
ID
ZDB-PUB-201212-2
Date
2021
Source
Chemosphere   263: 127911 (Journal)
Registered Authors
Garrity, Deborah
Keywords
Embryogenesis, Fathead minnow, Fibrates, Statins, Toxicology, Zebrafish
MeSH Terms
  • Zebrafish
  • Water Pollutants, Chemical*/toxicity
  • Pharmaceutical Preparations*
  • Animals
  • Morbidity
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Embryonic Development
  • Fibric Acids
  • Cyprinidae*
(all 9)
PubMed
33297010 Full text @ Chemosphere
Abstract
Antilipidemic drugs are routinely detected in effluent and surface waters downstream of wastewater treatment plants. A mixture exposure study with nine environmentally relevant antilipidemic drugs was performed with zebrafish (Danio rerio, ZF) and fathead minnow (Pimephales promelas, FHM) embryos to investigate the effects on sensitive embryologic stages. Zebrafish embryos were exposed nominally to: (a) 0.005 μM, (b) 0.05 μM, or (c) 0.5 μM of each drug in the mixture. Fathead minnow embryos were exposed nominally to: (a) 0.0005 μM, (b) 0.005 μM, or (c) 0.05 μM of each drug in the mixture. Several of the individual drug concentrations were within ranges previously found in the environment. Multiple metrics demonstrate that (a) exposure of ZF and FHM embryos to antilipidemic drugs during embryonic development results in lethal and sublethal effects, (b) ZF were more sensitive than FHM based on median lethal concentration (LC50 0.02 μM and 0.05 μM, respectively), but FHM exhibited more severe abnormal sublethal morphologies than zebrafish embryos, and (c) the sublethal effects differed between the two species. This model identified novel specific endpoints for assessing sensitive, sublethal effects of pharmaceuticals in the environment. Abnormal myofiber birefringence pattern, hemorrhage, and heart rate are not included in standard evaluations but each of these metrics demonstrated a dose-dependent response in this study. Results demonstrate risk to fish development with potential repercussions at the population level, especially if environmental concentrations increase.
Genes / Markers
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sd2TgTransgenic Insertion
    y1TgTransgenic Insertion
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      Sequence Targeting Reagents
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      Fish
      Antibodies
      Orthology
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRedEFGDsRed
      EGFPEFGEGFP
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      Citation
      Kingcade, A., Ahuja, N., Jefferson, A., Schaffer, P.A., Ryschon, H., Cadmus, P., Garrity, D., Ramsdell, H. (2021) Morbidity and mortality in Danio rerio and Pimephales promelas exposed to antilipidemic drug mixtures (fibrates and statins) during embryogenesis: Comprehensive assessment via ante and post mortem endpoints. Chemosphere. 263:127911.