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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ftimr:oai:imr.brage.unit.no:11250/2600500 2023-05-15T15:30:56+02:00 Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.) Bernhard, Annette Rasinger, Josef Daniel Betancor, Mónica B. Caballero, María José Berntssen, Marc Lundebye, Anne-Katrine Ørnsrud, Robin 2019 application/pdf http://hdl.handle.net/11250/2600500 https://doi.org/10.1371/journal.pone.0211128 eng eng Fiskeri- og havbruksnæringens forskningsfond: 901327 PLoS ONE. 2019, 14 (1), . urn:issn:1932-6203 http://hdl.handle.net/11250/2600500 https://doi.org/10.1371/journal.pone.0211128 cristin:1667577 36 14 PLoS ONE 1 Journal article Peer reviewed 2019 ftimr https://doi.org/10.1371/journal.pone.0211128 2021-09-23T20:15:03Z 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. publishedVersion Article in Journal/Newspaper Atlantic salmon Salmo salar Institute for Marine Research: Brage IMR PLOS ONE 14 1 e0211128 |
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Open Polar |
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Institute for Marine Research: Brage IMR |
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language |
English |
description |
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. publishedVersion |
format |
Article in Journal/Newspaper |
author |
Bernhard, Annette Rasinger, Josef Daniel Betancor, Mónica B. Caballero, María José Berntssen, Marc Lundebye, Anne-Katrine Ørnsrud, Robin |
spellingShingle |
Bernhard, Annette Rasinger, Josef Daniel Betancor, Mónica B. Caballero, María José Berntssen, Marc Lundebye, Anne-Katrine Ørnsrud, Robin Tolerance and dose-response assessment of subchronic dietary ethoxyquin exposure in Atlantic salmon (Salmo salar L.) |
author_facet |
Bernhard, Annette Rasinger, Josef Daniel Betancor, Mónica B. Caballero, María José Berntssen, Marc Lundebye, Anne-Katrine Ørnsrud, Robin |
author_sort |
Bernhard, Annette |
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.) |
publishDate |
2019 |
url |
http://hdl.handle.net/11250/2600500 https://doi.org/10.1371/journal.pone.0211128 |
genre |
Atlantic salmon Salmo salar |
genre_facet |
Atlantic salmon Salmo salar |
op_source |
36 14 PLoS ONE 1 |
op_relation |
Fiskeri- og havbruksnæringens forskningsfond: 901327 PLoS ONE. 2019, 14 (1), . urn:issn:1932-6203 http://hdl.handle.net/11250/2600500 https://doi.org/10.1371/journal.pone.0211128 cristin:1667577 |
op_doi |
https://doi.org/10.1371/journal.pone.0211128 |
container_title |
PLOS ONE |
container_volume |
14 |
container_issue |
1 |
container_start_page |
e0211128 |
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1766361408616792064 |