This review focuses on the current status of antibiotics use, effects on animal health and the environment, existing policies and regulatory mechanisms in the top 15 producing countries. Fifty papers were reviewed and represented the bulk of literature worldwide. We observed that 67 antibiotic compounds were used in 11 of the 15 countries between 2008 and 2018. Among these countries, 73% applied oxytetracycline, sulphadiazine and florfenicol. On average, countries used 15 antibiotics and the top users included Vietnam (39), China (33) and Bangladesh (21). On environmental and health risks, the review revealed sufficient evidence that directly links antibiotics use to food safety, occupational health hazards and antimicrobial resistance. Environmental risks included residue accumulation, aquatic biodiversity toxicity, microbial community selection for antibiotic resistance and the emergence of multi‐antibacterial resistant strains. Regarding policies, major players were the European Commission, the Food and Drug Administration, European Medicines Agency, Norwegian Veterinary Institute, the Norwegian Food Safety Authority, Codex and government ministries. In particular, the Norwegian Food Safety Authority and Norwegian Veterinary Institute demonstrated the most outstanding regulation mechanisms of antibiotics use in aquaculture that needs to be emulated. The future of aquaculture lies in guaranteeing the supply of safe aquatic products to the growing consumer market. Thus, international coordination of the policy and regulatory environment is needed, while increased investment in research for alternative aquatic health management strategies is essential. Future technologies should focus on the reduction of antibiotics use to safeguard the environment and ensure safety of consumers, feed industry and aquaculture workers.

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Copper is a common contaminant in aquatic environments, which may cause physiological dysfunction in marine organisms. However, the toxicity mechanisms of copper in marine bivalves is not fully understood. In this study, we applied an integrated approach that combines flow cytometry and Gas Chromatography-Mass Spectrometry (GC-MS)-based metabolomics to characterize cellular and molecular mechanisms of copper immunotoxicity in New Zealand Greenshell™ mussel (Perna canaliculus) haemolymph. Flow cytometric results showed significant increases in haemocyte mortality, production of reactive oxygen species and apoptosis (via alteration of caspase 3/7 and mitochondrial membrane potential) of haemocytes exposed to increasing total concentrations of Cu2+ (62.5, 125.0 and 187.5 μM) compared to a low Cu2+ concentration (25.0 μM) and control (0.0 μM). In addition to flow cytometric data, our metabolomics results showed alterations of 25 metabolites within the metabolite profile of Cu2+-exposed haemolymph (125 μM) compared to those of control samples. Changes in levels of these metabolites may be considered important signatures of oxidative stress (e.g., glutathione) and apoptosis processes (e.g., alanine, glutamic acid). This study provides insights into the cellular and molecular mechanisms of oxidative stress and apoptosis in marine bivalves and highlights the applicability and reliability of metabolomic techniques for immunotoxicological studies in marine organisms.

Polyinosinic:polycytidylic acid [poly (I:C)] was administered in vivo to Chinook salmon (Oncorhynchus tshawytscha) post‐smolts to determine the immune responses on haematological and cellular functional parameters, including spleen (SP), head kidney (HK) and red blood cell (RBC) cytokine expression, as well as serum metabolomics. Poly (I:C) in vivo (24 h exposure) did not affect fish haematological parameters, leucocyte phagocytic activity and phagocytic index, reactive oxygen species and nitric oxide production. Gas chromatography–mass spectrometry–based metabolomics revealed that poly (I:C) significantly altered the serum biochemistry profile of 25 metabolites. Metabolites involved in the branched‐chain amino acid/glutathione and transsulphuration pathways and phospholipid metabolism accumulated in poly (I:C)–treated fish, whereas those involved in the glycolytic and energy metabolism pathways were downregulated. At cytokine transcript level, poly (I:C) induced a significant upregulation of antiviral ifnγ in HK and Mx1 protein in HK, SP and RBCs. This study provides evidence for poly (I:C)–induced, immune‐related biomarkers at metabolic and molecular levels in farmed O. tshawytscha in vivo. These findings provide insights into short‐term effects of poly (I:C) at haematological, innate and adaptive immunity and metabolic levels, setting the stage for future studies.