Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.).
Ethoxyquin (EQ; 6-Ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline) has been used as an antioxidant in feed components for pets, livestock and aquaculture. However, possible risks of EQ used in aquafeed for fish health have not yet been characterized. The present study investigated the toxicity and dose-...
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ftdoajarticles:oai:doaj.org/article:b98a4aaca8d140aba002d7d441b80d7f 2023-05-15T15:31:02+02:00 Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). Annette Bernhard Josef D Rasinger Monica B Betancor Maria José Caballero Marc H G Berntssen Anne-Katrine Lundebye Robin Ørnsrud 2019-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0211128 https://doaj.org/article/b98a4aaca8d140aba002d7d441b80d7f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pone.0211128 https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0211128 https://doaj.org/article/b98a4aaca8d140aba002d7d441b80d7f PLoS ONE, Vol 14, Iss 1, p e0211128 (2019) Medicine R Science Q article 2019 ftdoajarticles https://doi.org/10.1371/journal.pone.0211128 2022-12-31T05:33:12Z Ethoxyquin (EQ; 6-Ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline) has been used as an antioxidant in feed components for pets, livestock and aquaculture. However, possible risks of EQ used in aquafeed for fish health have not yet been characterized. The present study investigated the toxicity and dose-response of subchronic dietary EQ exposure at doses ranging from 41 to 9666 mg EQ/kg feed in Atlantic salmon (Salmo salar L.). Feed at concentrations higher than 1173 mg EQ/kg were rejected by the fish, resulting in reduced feed intake and growth performance. No mortality was observed in fish exposed to any of the doses. A multi-omic screening of metabolome and proteome in salmon liver indicated an effect of dietary EQ on bioenergetics pathways and hepatic redox homeostasis in fish fed concentrations above 119 mg EQ/kg feed. Increased energy expenditure associated with an upregulation of hepatic fatty acid β-oxidation and induction and carbohydrate catabolic pathways resulted in a dose-dependent depletion of intracytoplasmic lipid vacuoles in liver histological sections, decreasing whole body lipid levels and altered purine/pyrimidine metabolism. Increased GSH and TBARS in the liver indicated a state of oxidative stress, which was associated with activation of the NRF2-mediated oxidative stress response and glutathione-mediated detoxification processes. However, no oxidative DNA damage was observed. As manifestation of altered energy metabolism, the depletion of liver intracytoplasmic lipid vacuoles was considered the critical endpoint for benchmark dose assessment, and a BMDL10 of 243 mg EQ/kg feed was derived as a safe upper limit of EQ exposure in Atlantic salmon. Article in Journal/Newspaper Atlantic salmon Salmo salar Directory of Open Access Journals: DOAJ Articles PLOS ONE 14 1 e0211128 |
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Medicine R Science Q Annette Bernhard Josef D Rasinger Monica B Betancor Maria José Caballero Marc H G Berntssen Anne-Katrine Lundebye Robin Ørnsrud Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). |
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Medicine R Science Q |
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Ethoxyquin (EQ; 6-Ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline) has been used as an antioxidant in feed components for pets, livestock and aquaculture. However, possible risks of EQ used in aquafeed for fish health have not yet been characterized. The present study investigated the toxicity and dose-response of subchronic dietary EQ exposure at doses ranging from 41 to 9666 mg EQ/kg feed in Atlantic salmon (Salmo salar L.). Feed at concentrations higher than 1173 mg EQ/kg were rejected by the fish, resulting in reduced feed intake and growth performance. No mortality was observed in fish exposed to any of the doses. A multi-omic screening of metabolome and proteome in salmon liver indicated an effect of dietary EQ on bioenergetics pathways and hepatic redox homeostasis in fish fed concentrations above 119 mg EQ/kg feed. Increased energy expenditure associated with an upregulation of hepatic fatty acid β-oxidation and induction and carbohydrate catabolic pathways resulted in a dose-dependent depletion of intracytoplasmic lipid vacuoles in liver histological sections, decreasing whole body lipid levels and altered purine/pyrimidine metabolism. Increased GSH and TBARS in the liver indicated a state of oxidative stress, which was associated with activation of the NRF2-mediated oxidative stress response and glutathione-mediated detoxification processes. However, no oxidative DNA damage was observed. As manifestation of altered energy metabolism, the depletion of liver intracytoplasmic lipid vacuoles was considered the critical endpoint for benchmark dose assessment, and a BMDL10 of 243 mg EQ/kg feed was derived as a safe upper limit of EQ exposure in Atlantic salmon. |
format |
Article in Journal/Newspaper |
author |
Annette Bernhard Josef D Rasinger Monica B Betancor Maria José Caballero Marc H G Berntssen Anne-Katrine Lundebye Robin Ørnsrud |
author_facet |
Annette Bernhard Josef D Rasinger Monica B Betancor Maria José Caballero Marc H G Berntssen Anne-Katrine Lundebye Robin Ørnsrud |
author_sort |
Annette Bernhard |
title |
Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). |
title_short |
Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). |
title_full |
Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). |
title_fullStr |
Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). |
title_full_unstemmed |
Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.). |
title_sort |
tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in atlantic salmon (salmo salar l.). |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pone.0211128 https://doaj.org/article/b98a4aaca8d140aba002d7d441b80d7f |
genre |
Atlantic salmon Salmo salar |
genre_facet |
Atlantic salmon Salmo salar |
op_source |
PLoS ONE, Vol 14, Iss 1, p e0211128 (2019) |
op_relation |
https://doi.org/10.1371/journal.pone.0211128 https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0211128 https://doaj.org/article/b98a4aaca8d140aba002d7d441b80d7f |
op_doi |
https://doi.org/10.1371/journal.pone.0211128 |
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PLOS ONE |
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14 |
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e0211128 |
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1766361533458153472 |