Nanotechnology in aquaculture: Applications, perspectives and regulatory challenges

Carlos Fajaro, Gonzalo Martinez-Roriguez, Julian Blaso, Juan Miguel Manera,Bolaji Thomas, Maros De Donato

aSchool of Tourism and Maritime Technology, Polytechnic of Leiria (MARE-IPLeiria), Santuario de Nossa Senhora dos Remedios, Campus 4, Peniche, 2520-641,Portugal

bDepartment of Biology, Faculty of Marine and Environmental Sciences, Instituto Universitario de Investi-gación Marina (INMAR), Campus de Excelencia Internacional del Mar (CEI⋅MAR), University of Cadiz (UCA), Puerto Real, 11519, Spain

cInstitute of Marine Sciences of Andalusia (ICMAN), Department of Marine Biology and Aquaculture, Spanish National Research Council (CSIC), Puerto Real, 11519,Spain

dDepartment of Biomedical Sciences, Rochester Institute of Technology, Rochester, 14623, USA

eTecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Queretaro, 76130, Mexico

Keywords:

Health management

Nano-regulation

Nutraceuticals

Preservation of seafood

Risk assessment

A B S T R A C T

Aquaculture is considered one of the most important food production systems both in terms of economic impact and food security, and the ongoing development of this industry is a key factor in the strategy to guarantee global nutritional safety. Nowadays, different types of nanotechnology-based systems have been employed to increase its production, efficiency and sustainability. Recent efforts have been made in the fields of health management,enhancement of fish and shell fish development by dietary supplementation with nutraceuticals, but also in the processing and preservation of seafood and water treatment, among others. Therefore, nanotechnology has a significant role to play in the improvement of the efficiency and the environmental impact of this industry. Given this perspective, we propose to review the current situation of nanotechnology in the field of aquaculture and fisheries, emphasizing not only in current applications, and future prospects, but also in the ethical and governance aspects associated with this topic.

1.Introduction

The United States National Nanotechnology Initiative (NNI) de fine nanotechnology as the “understanding and control of matter at the nanoscale, at dimensions between approximately 1 and 100 nm, where unique phenomena enable novel applications” (https://www.nano.gov/nanotech-101/what) (Fig. 1). Nanotechnology has enormous potential to provide innovative improvements to aquaculture systems to reduce costs,increase efficiency and to reduce our impact on the environment, as a necessity impacting our ability to feed the 7 billion plus inhabitants of the planet. China has been at the forefront of rapid development and deployment of nanotechnology in the agri-food sector, applications that would only be described as successful if the products satisfy the demands of quality, reduced cost, environmental sustainability and low risk to human health (Chena & Yadab, 2011). Nowadays, nanotechnology is a multi-billion and rapidly expanding industry, exemplified by the more than a thousand products containing nanomaterials currently in the market. Since the past decade, over 300 nanofood products have become available in international markets (Ramsden, 2018), with the economic impact of nanotechnology industries estimated to be at least $ 3 trillion in 2020, in addition to employing about 6 million workers (He et al.,2019).

The global nanotechnology market applied to food sector was recently projected to increase at an annual rate of more than 24% during the period 2019–2023, reaching $ 112.48 billion, the growing applications in nutraceuticals primarily responsible for this market boost(Technavio, 2019). Currently, the available information suggests that nanofood sector is led by the United States, followed by China, Japan and the European Union (EU) (Chaudhry et al., 2017; Thiruvengadam et al., 2018). United States leads this group with the world largest funding source for nanotechnology research, a 4-year plan of investment of $3.7 billion, channeled through its National Nanotechnology Initiative (NNI) (Meghani et al., 2020; Thiruvengadam et al., 2018).Nowadays, some of the top players in this industry are companies like AQUANOVA (Germany), BASF (Germany), NanoPack (Belgium), and PEN (USA).

Nanotechnology incorporates diverse disciplines such as physics,chemistry, biotechnology, and engineering (Chandra, 2016), and operates at the 1–100 nm range, several dimensions of structural elements,crystallites, molecules and clusters are manifest in nanomaterials(Fig. 2), which includes zero dimension (nanoparticles, nanoclusters,and quantum dots), one dimension, (carbon nanotubes and multiwalled nanotubes), two dimensions (graphene layers and ultrathin films), and three dimensions (nanostructured materials). Different forms and shapes of nanoparticles are used, such as dendrimers (Wu et al., 2015a),nanocapsules (Torchilin, 2006), nanospheres (Donbrow, 1991), nanotubes (Reilly, 2007), etc. Additionally, nanomaterials have been reported with many advantages; for example, tissue-specific targeting,dose and toxicity reduction, as well as increased bioavailability, drug efficacy, and reduction of secondary adverse effects (Shah & Mraz, 2019;Toyokawa et al., 2008; Xu et al., 2018a). The physiochemical properties of nanomaterials result in its wide application on food preservation,water treatment, and healthcare, among others (Baranwal et al., 2018;Ogunkalu, 2019).

Fig. 2.The different dimensions of nanomaterials currently being developed.

Nanomaterials could be synthetized arranging atom by atom (bottom up process) or converting large materials to nanoscale (top down process), with physical, optical, chemical, magnetic and electric properties facilitating these processes (Roy et al., 2012). The main type of nanomaterials includes nano-metals, metal oxides, carbon nanotubes and carbon spheres, as well as composites such as quantum dots,nano-ceramics and nanoshells (Boxall et al., 2007; Stone et al., 2010),though there are potentially unlimited number of chemical elements that can be used to produce nanomaterials. Nanomaterials are now also emerging with complex three-dimensional shapes, and/or containing several different chemical substances (Handy, 2012, pp. 1–29). On the other hand, the utilization of nanoparticles to advance aquaculture and the seafood industry is gaining enormous momentum. Aquaculture is the food industry showing the fastest growth and produces more than 50% of seafood used for food (Souza et al., 2017; Hussain et al., 2019). Fish production worldwide reached about 180 million tons in 2018, with an estimated total first sale value of $ 401 billion, of which 82 million Tm,worth $ 250 billion, came from aquaculture production; food fish consumption per capita grew from 9.0 kg (1961) to 20.5 kg (2018), with an average rate of around 1.5%/year (FAO, 2020; Shah & Mraz, 2019).Thus, aquaculture can be one of the greatest contributing industry to the Sustainable Development Goals for 2030 (FAO, 2018). Furthermore,aquaculture is a key activity generating jobs for traditional fishing families, especially important in developing countries, engaging approximately 20.5 million people around the world (Sibaja et al., 2019;FAO, 2020). However, environmental degradation, chemical contamination, suboptimal nutrition and disease prevalence, are among the factors that negatively impact this sector for the achievement of global food security (Shah & Mraz, 2019).

Nanotechnology has a wide range of applications in aquaculture and could significantly help transform this industry (Fig. 3). Between its current applications we can find the detection and control of pathogens,water treatment, sterilization of ponds, efficient delivery of nutrients and drugs (Jimenez-Fernandez et al., 2014; Bhattacharyya et al., 2015;Huang et al., 2015; Sibaja-Luis et al., 2019). For example, DNA-nano vaccines are been used to improve fish immune system. Similarly, iron nanoparticles can also be used to improve fish growth (Mohammadi and Tukmechi, 2015).

Fig. 3.Current key applications of nanotechnology in the aquaculture industry.

Nowadays, there are numerous possibilities for the future application of these technologies. Inside the agri-food sector, research in nanomaterials applications for delivery systems has been carry out using nanoparticles, micelles, liposomes, biopolymers, emulsions, proteincarbohydrate complexes, dendrimers, and solid nano-lipid particles,among others. The main properties that provide advantages of these nanomaterials include high absorption and bioavailability, better dispersion and solubility, improving stability against environmental degradation during the food processing, as well as controlled release kinetics (Chen et al., 2006; Ogunkalu, 2019; Pathakoti et al., 2017).Additionally, using nanomaterials for delivery systems can improve the nutritional profiles of feed and feeding conversion rate (Bhattacharyya et al., 2015). These advantages improve the efficiency, reduce waste and financial burden, and improve production yield and quality (Chena &Yadab, 2011).

Compared to other technologies, delivery of molecules through nanotechnology applications can be more effective in preventing/treating diseases, through precise delivery and controlled release of drugs and vaccines, decreasing risks associated to health and environmental factors and reducing the use of chemicals. Nanoparticles for target delivery may allow new drug administration methods which are faster, non-intrusive, and more cost effective. Furthermore, treatment that can prevent diseases, combining diagnostics and therapy in a single step (theragnostics), will improve the effectiveness of disease treatment and significantly lower the costs (Chena & Yadab, 2011; Morris, 2009).

Nanotechnology also includes improvement of fish packaging techniques, and enhancement of quality in terms of flavor, texture, odor,appearance, taste, as well as improving fish nutrients absorption.Nanotechnology is also applied to improve bioavailability (including functional compounds), encapsulation and monitoring the release of microencapsulated antimicrobials in packaging, slowing down the decomposition process, improving stability and shelf-life of delicate ingredients. Another application of nanoparticles includes its bacteriostatic properties to create microbial resistant surfaces. For example,silver nanoparticles have been used for reduction of pathogens and extension of shelf life of meat products in diverse sectors in the agri-food industry (Ogunkalu, 2019). Nevertheless, the disposal of nanoparticles also adds concerns to the environment and health (Otles & Yalcin,2008), since absorption of these particles could have a detrimental effect on replication of DNA and resulting in genetic mutations (Suppan, 2011,pp. 3–20). For nanotechnology to be sustainable and used for more applications, the life cycle and shelf-life of nanomaterials have to be studied to consider potential health and environmental risks that they may have, including exposure, uptake, accumulation, release, and deposition (Handy, 2012, pp. 1–29).

Given this perspective, the main goal of this review is focused on exposing a broad compendium of information about, not only the main uses and applications of biotechnology in the field of aquaculture; but also on the perspectives about the regulatory and legislative aspects associated with these technologies.

2.Drug delivery for health management

Disease outbreak is one of the main obstacles for the sustainability and development of aquaculture (Rather et al., 2011; Sibaja-Luis et al.,2019; Yang et al., 2021). In this context, nanotechnology has an enormous role to play, linked to provide novel perspectives related to disease diagnosis and health management (Handy, 2012, pp. 1–29). Some strategies involve solid core drug delivery systems, which imply coating a solid nanoparticle by a fatty acid shell to protect the drug (Fig. 4). This technique is especially successful in the case of labile or thermo-sensitive drugs, (Mitchell & Trivedi, 2010). Moreover, poriferous nanomaterials can be used as a pharmaceutical delivery matrix. For instance, for the controlled release of drugs, mesoporous silica particles can be employed(Stromme et al., 2009). Oral nano-delivery systems linked to nanoparticles have been used for many reasons, among others, the enhancement in the control of drug release (Eldridge et al., 1990),including direct target tissue release (Jani et al., 1990), bioavailability of pharmaceuticals with low absorption rates (Florence et al., 1995),stabilization of drugs by increased residence time in the gut (Peters &Brain, 2009), as well as improved absorption capability, granted by a higher dispersion rate at the molecular level (Mohanraj & Chen, 2006).

Fig. 4.Different nanoparticles being investigated in aquaculture for drug delivery and targeted therapy, as well as the advantages of using nanoparticles.

Alginate is a naturally found polymer made from β-D-mannuronic acid (M) and α-L-guluronic acid (G) seen in some brown algae, and bacteria (Shah & Mraz, 2019) and can be used to produce nanoparticles efficiently and scalable by emulsification (Reis et al., 2017). Reports from several sources presented alginate, not only as an antigen adjuvant(Borges et al., 2008; Tafaghodi et al., 2007), but also as a survival and weight promoter of fish (Chiu et al., 2008; Fujiki et al., 1994). Moreover,alginate can enhance immune response in the brown-marbled grouper(Epinephelus fuscoguttatus), and the Asian carp (Cyprinus carpio), as well as enhanced immunological system of the brown-marbled grouper and the orange-spotted grouper (E. coioides) against iridovirus andStreptococcussp., and for the turbot (Scophthalmus maximus) againstV. anguillarum(Cheng et al., 2008; Huttenhuis et al., 2006; Skjermo &Bergh, 2004; Yeh et al., 2008). A combination of chitosan-alginate has been effectively used for oral vaccination in rainbow trout (Oncorhynchus mykiss) againstLactococcus garvieaeandStreptococcus iniae,increasing the survival after challenge tests and the immunological response, compared to the non-coated vaccine and control groups(Halimi et al., 2019).

Moreover, DNA nanovaccines, short strands of DNA within nanocapsules, have been used in the aquaculture industry to induce an immune response in fishes. Iron nanoparticles have shown to accelerate fish development, linked to a drug delivery with programmed release,are becoming true very fast by this approach (Hussain et al., 2019). For example, nano encapsulated vaccines have been successfully used against the bacteriumListonella anguillarumin Asian carp (Bhattacharyya et al., 2015) and rainbow trout (Oncorhynchus mykiss) (Mongillo,2007; Ogunkalu, 2019).

Chitosan is a polysaccharide composed of randomly distributed β–linked D-glucosamine andN-acetyl-D-glucosamine that can be naturally found in the exoskeleton of crustaceans and insects (Elieh-Ali-Komi& Hamblin, 2016). It has unique features, such as being non-toxic and biodegradable, bio-adhesive, and biocompatible. Due to this, formulations based on chitosan, mostly as emulsions, have been use for drug delivery, edible coatings in aquaculture species, as well as in human medical applications such as surgical procedures or dentistry (Shah &Mraz, 2019).

There are lot of examples of successfully encapsulation and delivery by chitosan-based systems in aquaculture. In this sense, treatment methods have been developed againstVibrio parahaemolyticusin the blackhead seabream (Acanthopagrus schlegelii) (Li et al., 2013),Philasterides dicentrarchiin the turbot (S. maximus) (Leon-Rodrıguez et al.,2013), andVibrio anguillarumin Asian sea bass (Lates calcarifer) (Kumar et al., 2008). Both DNA and RNA, have been successfully encapsulated and delivered following this system. For example, dietary RNA has been used in rohu (Labeo rohita) (Ferosekhan et al., 2014), as well as inactive particles of the viral haemorrhagic septicaemia virus (VHSV) in Japanese flounder (Paralichythys olivaceus) (Kole et al., 2019). Furthermore,Kitiyodom et al. (2019) have reported the enhanced efficacy of immersion vaccination in tilapia (Oreochromissp.) against columnaris disease by a chitosan-coated mucoadhesive nanovaccine. Additionally,chitosan-coated membrane vesicles (cMVs) from the intracellular fish pathogenPiscirickettsia salmoniswere, injected into adult zebra fish (Danio rerio), provided a significant protection with increased survival and induced increased immune response (Tandberg et al., 2018).

In this sense, Rajeshkumar et al. (2009) found that chitosan-encapsulated DNA construct containing the VP28 gene of white spot syndrome virus (WSSV) were able to significantly increase survival when challenged with the virus, compared to the 100% mortality of the control. However, the relative survival was reduced from 85 to 50% when the challenge was carried out from 7 to 30 days posttreatment,with a reducing effect due to the lack of memory response of the crustacean immune system.

Another biodegradable polymer, polylactidecoglycotidic acid(PLGA) has been largely used for encapsulation and delivery of different compounds in fish (Shah & Mraz, 2019). For example, a DNA vaccine encapsulated in PLGA showed improved immunological response against lymphocystis (Tian & Yu, 2011). Additionally, Behera et al.(2010) have found that PLGA encapsulated antigens fromAeromonas hydrophila, used as a vaccine in rohu, have produced to a strong immune-stimulatory and antibody response, both 21- and 42-days post-immunization.

Yun et al. (2017) used PLGA microparticles to carryA. hydrophilacells that were previously killed by formalin treatment, as a way to deliver antigens to pond loach (Misgurnus anguillicaudatus) and common carp (C. carpio). When they were challenged withA. hydrophilathe fishes treated with PLGA-A. hydrophilashowed higher survival and increased innate and adaptive immune responses than the group treated just with the killedA. hydrophila, which could potentially induce higher and more lasting immune responses than the antigens alone. Additionally, mass vaccination can be achieved using nanocapsules resistant to digestion and degradation. Both, oral administration and site-specific release of the active agent, will reduce the effort and cost related to disease management, leading to more sustainable practices (Rather et al., 2011).

Another formulation in the form of liposomes, which are made out of phospholipids, has been largely used in several areas of aquaculture. In the case of the Asian carp, liposome-encapsulated antigens ofAeromonas salmonicida, an experiment showed higher survival and decrease skin ulcers, when compared to the control group (Irie et al., 2005). Moreover,in other experiments,A. hydrophilaantigens emulsified in liposomes improved the serum antibody, which will enhance immunity response,in the common carp (Shah & Mraz, 2019; Yasumoto et al., 2006). More recently, Malheiros et al. (2020) have reported nanoemulsions with oleoresin ofCopaifera reticulata(Leguminosae) against monogeneans parasites on the gills of Tambaqui (Colossoma macropomum). They found that the oleoresin without nanoemulsions showed an efficacy of 100% only at 600 mg/L or higher concentration whereas the nanoemulsioned oleoresin showed efficacy of 100 after 30 min of exposure at a concentration of 200 mg/L). Additionally, all the fish died after 2 h of exposure in all the concentrations tested (200–1000 mg/L) when applied alone,while all of the ones treated with nanoemulsioned oleoresin were alive at all concentrations tested (50–250 mg/L).

In last few years, controlled release delivery systems and diagnostic sensor based on nanoparticles have been developed to change their properties and structure according to environmental stimulus such temperature, ionic strength, pH, or enzymatic activity. For example, in the pharmaceutical industry, pH sensitive nanoparticles have been used for the delivery of anticancer molecules (Nile et al., 2020). Moreover,McClements (2017) reported lipid nanoparticles carrying bioactive compounds that can be broken down by the contact with lipases,therefore, the bioactive compound can be released under gastrointestinal disorder conditions. Recently, Lee et al. (2020) developed an interesting method that can be potentially used as oral vaccines in aquaculture. To probe their approach, they used a stimulator of the immune system, in this case, the antigen fromStreptococcus parauberis(inactivated by a formalin treatment); which was encapsulated by alginate beads, was used as a model. In order to control both encapsulation efficiency and release at the target organ (intestine), they crossed-linked the beads with clay nanoparticles. The entire system is focused on storage under gastric condition and release under intestinal conditions, responding to the pH level. This could be a very effective approach to treat only affected organisms in a population under culture,using the treatment only when needed.

3.Nanosensors for pathogen detection

Nanobiosensor systems are currently being developed to allow the detection of very low concentrations not only of parasites, bacteria and viruses, but also of polluting elements in the water (Chen et al., 2016).This is particularly important in outbreaks at commercial aquaculture systems, since it can take too much time before the etiological agent causes an impact so that its presence is identified, delaying the treatment to control the pathogen, creating an important economic impact. In this regard, nanotechnology holds the potential to overcome this challenge through the early detection and eradication of pathogens.

Currently, nanosensors are able to detect a wide range of pathogenic agents. For example, using electrical nanosensors, it is feasible to detect single virus particles (Patolsky et al., 2004). Moreover, it has been reported that immuno-targeted gold nanoparticles are able to be functionalized with an antibody targeted to a particular biomolecule of interest, such as immunoglobulin G-capped gold nanoparticles, to bind specifically to antibodies generated againstStaphylococcus pyrogenes,andS. aureus, among others (Roy et al., 2012). Nanosensors are also used for fishpond cleaning and stock scrutiny, such as those based on carbon nanotubes, which are highly sensitive for the detection of traces of pathogens like viruses, parasites, and bacteria; and also heavy metals,both from food and water (Hussain et al., 2019).

Tracking-nanosensors, with locators that relay data about geolocalization and fish health status, have been reported, through the use of big data analysis technology, that allows the control of individual fish or in the development of intelligent cage systems (Sekhon, 2014;Hussain et al., 2019). A chip that had incorporated a nanoscale radio circuit linked to an embedded identification code, called nano-barcode,has been reported as an individual tracking device, in such a way that the information held in the tags can be scanned from the distance to identify them automatically. Such tags could be used not only as a tracking device, but also to monitor feeding behavior, swimming pattern, and even the metabolism of animals. Through the inclusion of nano-barcoding, both exporters and processing industry are able to monitor the source of a particular product, as well as to track the delivery status. Moreover, these nanosensors, coupled with synthetic DNA tagged with color coded probes, nano-barcode systems could be used not only to identify pathogens, but also monitoring leakages and temperature changes, and other parameters; therefore, enhancing the product quality (Rather et al., 2011).

4.Microbial disinfection

Many of metal NPs have been used for disease prevention and treatment, such as silver, titanium, cupper, among others. Metal NPs have different modes of action against bacteria, of which, one of the strongest effects is against the cell membrane and cell wall by attaching to them by electrostatic interaction and being able to disrupt them(Fig. 5). They can also disrupt the ion transport by association with ions and ion channels. This NPs can cause double strand breaks of the DNA,interfere with the ribosome assembly and the enzymatic activity, via electrostatic interactions. Metal NPs are also known to trigger a higher oxidative stress state increasing the amount of reactive oxygen species(ROS) which can damage proteins, lipids, and DNA.

Fig. 5.Effects of the metal nanoparticles (NPs) on the different elements of bacteria, when used for microbial disinfection, disease treatment and prevention. Metal NPs can attach and disrupt both the cell membrane and the cell wall,as well as can disrupt the ion transport by association with ions and ion channels. These NPs can cause double strand breaks of the DNA, interfere with the ribosome assembly and the enzymatic activity, via electrostatic interactions.Metal NPs can also trigger a higher oxidative stress state increasing the amount of reactive oxygen species (ROS) which can damage proteins, lipids, and DNA.

Colloidal silver nanoparticles are one of the main nanotechnology products used against a wide spectrum of pathogens, including viruses,parasites, fungi, and bacteria. Silver is considered one of the most promising nanomaterials among the oligo-dynamic metallic nanoparticles, due to its wide-range effects on different microbial species,ease application in different forms, its crystallographic structure, high surface exposure compared to its volume, and compatibility to several compounds (Nangmenyi & Economy, 2014). The antimicrobial activity is related to the oxidation capacity to DNA and proteins with highly damaging effects. For example, silver nanoparticles can destroy strains of methicillin-resistantS. aureus(Jeong et al., 2005).

Microbial elimination protocols have also been develop using visible light photo-catalysts mediated by nanoparticles of metal oxides, as well as nano-porous fibers and foams (Li et al., 2014). Their effect is not limited to microbial elimination, but also for elimination of organic pollutants from the pharmaceuticals and cosmetics industry (Chena &Yadab, 2011). Titanium dioxide nanoparticles, for example, have a strong anti-bacterial activity, capable of destroying fish pathogensin vitro(Cheng et al., 2009), and their actions have been confirmed as a strong immune modulator of fish neutrophil function (Jovanovic et al.,2011). Currently, a commercially available nanotechnology device,named NanoCheck, can be used for cleaning fishponds through lanthanum based particles (40 nm size), which can inhibit algae growth by absorbing phosphates from the water (Rather et al., 2011).

Korni & Khalil (2017) reported that ginger nanoparticles are able to prevent infection by motileAeromonas septicaemiain the Asian carp fingerlings. Rather et al. (2017) reported that silver nanoparticles synthesized byAzadirachta indica(neem) have potential antibacterial and immunomodulatory activity in mrigal (Cirrhinus mrigala) fingerlings challenged withA. hydrophila. More recently, Erdem et al. (2018)demonstrated the antibacterial efficacy of silver nanoparticles synthetized troughAeromonas sobriaagainstA. hydrophila. This raised the possibility to improve sanitary management through the use of more environmentally friendly antimicrobial agents (Shah & Mraz, 2019).

In this regard, it is important to highlight the recently published work by Kepiro et al. (2020), which establishes the conceptual design of protein pseudocapsids exhibiting a broad spectrum of antimicrobial activities. In contrast to conventional antibiotics, these pseudocapsids are highly effective against diverse bacterial strains. This method can eliminate antibiotic-resistant bacteriain vivowithout causing toxicity.Pseudocapsids adopt an icosahedral structure that is polymorphic in size, but not in shape, and that is available in both D and L epimeric configurations. These authors demonstrate that such pseudocapsids can inflict a fast and irreversible harm to bacterial cells.

5.Treatment of pollutants in the water

Nanotechnology has also been used to treat water pollution, which is one of the main problems in aquaculture. Water treatment, related to the photo-catalysis and adsorption efficiencies of nanomaterials, producing effective and inexpensive approaches to water purification. For example, to eliminate arsenite contamination from groundwater, magnetic konjac glucomannan aerogels has been developed with green step features (Ye et al., 2016). Nevertheless, graphene nano-sheets and graphene oxide, linked to removal of several types of pollutants from water,have attracted tremendous attention in last few years (Liu et al., 2016;Motamedi et al., 2014). Graphene oxide-titanium oxide nanocomposite have been used for adsorption, removal of heavy metal and organic compounds from residual water (Atchudan et al., 2017; Hu et al., 2013).Features such as low cost, non-toxic, efficient photo-catalyst,biologically and chemically stable, point out titanium oxide as a promising candidate for residual water treatment. Moreover, several studies have been carried out to study the photocatalytic activity of titanium dioxide, showing to be capable of killing a wide range of Gram-negative and Gram-positive bacteria, filamentous and unicellular fungi, algae,protozoa, mammalian viruses and bacteriophages (Foster et al., 2011).The action resides in the production of reactive oxygen radicals and peroxice that can destroy cell walls and membranes. Nanoparticles can degrade antibiotics by the production of reactive oxygen species.Through the application of similar techniques, it was possible to use iron nanoparticles to break down polychlorinated biphenyls and dioxins into less toxic carbon compounds from ground water (Majumder & Dash,2017).

6.Delivery of dietary supplements and nutraceuticals

One of the main underlying concepts behind the idea that nanoparticles can improve the fish development is based on their ability to increase the quantity of nutrients absorbed across the digestive tract.Micronutrients, in the form of nanoparticles, incorporated in aquaculture feeds, can penetrate in cells more efficiently, and therefore, rise absorption rate (Fig. 6) (Ogunkalu, 2019; Zhou et al., 2009). This has been demonstrated in sturgeon and young carp, which showed faster growth rates when fed with iron nanoparticles (ETC, 2003). A similar result was presented in the case of nano-selenium, which showed to be more effective than organic seleno-methionine. Nano-selenium supplemented diets can enhance muscle selenium concentration, antioxidant status, relative gain rate, and final weight of crucian carp (Carassius auratus gibelio) (Zhou et al., 2009).

Fig. 6.Use of microelements in the form of nanoparticles to be included in aquaculture feeds and the effects seen in shrimp and fish.

Significant improvement can be observed when adding selenium nanoparticles in the feed, in order to enhance the antioxidant defense system and growth (Ashouri et al., 2015). Moreover, in gilthead seabream (Sparus aurata), manganese, zinc, and selenium nanoparticles supplementation in early diets, enhanced bone mineralization and stress resistance (Izquierdo et al., 2017). In rainbow trout, diet supplemented withLactobacillus caseiand iron nanoparticles, as a probiotic, notably enhanced growth parameters (Mohammadi et al., 2015), whereas diet with manganese oxide nanoparticles (16 mg/kg), highly improved antioxidant defense system and growth in freshwater prawn (Macrobrachium rosenbergii) (Asaikkutti et al., 2016). Furthermore, the addition of copper nanoparticles into the feed, also notably increased non-specific immune response, antioxidant metabolic enzyme levels,digestive enzyme activities, biochemical constituents, and growth; both in red sea bream (Pagrus major) (ElBasuini et al., 2017) and freshwater prawn (Muralisankar et al., 2016).

Additionally, phytochemically synthesized gold nanoparticles byAzolla microphylla, have been recommended to effectively reduce hepatic damage seen in the Asian carp due to acetaminophen present in the water as a contaminant (Kunjiappan et al., 2015). Those gold nanoparticles highly improve the levels of oxidative stress markers, reduced hepatic ions, metabolic enzymes, hepatotoxic markers, abnormal liver histology, altered tissue enzymes, etc. In the Siberian sturgeon (Acipenser baerii),Aloe verananoparticles have also been reported, to enhance body composition, survival rate, and growth (Sharif et al.,2017).

Nanotechnology also has been employed in attempting to improve the bioavailability and increasing the retention span of natural bioactive compounds (Cui et al., 2009). For example, encapsulation of curcumin in nanoparticles have been reported in the form of phospholipids(Semalty et al., 2010), micelles (Takahashi et al., 2009; Wang et al.,2009), liposomes (Letchford et al., 2008), hydrogels (Shah et al., 2008),among others (Das et al., 2010). More recently, it was possible to encapsulate curcumin in chitosan nanoparticles stabilized trough Pickering emulsion, in order to improve the curcumin shell-life (Shah et al.,2016). In the case of hydrophobic bioactive compounds, Pickering emulsion is considered the best encapsulation approach, in terms of improving shelf-life (Matos et al., 2016; Shah & Mraz, 2019; Xu et al.,2018b), because of the stabilization by solid particles (nutrients in this case).

These emulsions present superior characteristics in comparison with conventional emulsions (Dickinson, 2010), in terms of having low or no toxicity, better reproducibility and biocompatibility, ease and scalable production (Wu & Ma, 2016), and to improve stability (Binks, 2007).Moreover, both formulation and design of these emulsions improve the delivery of biological compounds in the digestive tract (Liu & Tang,2016; Matos et al., 2018; Ngwabebhoh et al., 2018; Shao et al., 2018;Winuprasith et al., 2018). Currently, many types of colloidal particles have been used in the production of Pickering emulsions, where solid particles help stabilizing the emulsion. For example, starch-based Pickering emulsions have been used to deliver compounds (Marku et al., 2012), such as hydrophobic antifungal compounds (Cossu et al.,2015; Leclercq & Nardello-Rataj, 2016).

Nano-crystalline, self-stabilized Pickering emulsion has great potential to use it to drug delivery and release, especially with compounds that have low solubility (Yi et al., 2017). More recently, oil Pickering emulsions stabilized using cellulose nanocrystals with oregano essential oil were used to improve its antibacterial properties againstE. coli, B.subtilis, S. aureus,andS. cerevisiae(Zhou et al., 2018). Additionally, in order to develop an antibacterial delivery system againstE. coli,Zein/Arabic-gum nanoparticle-stabilized Pickering emulsion was produced with thymol (Li et al., 2018; Shah & Mraz, 2019). More recently,Baldissera et al. (2020a; b), have reported that dietary supplementation with nerolidol-loaded nanospheres reduced bacterial loads, increased survival rates, and prevented oxidative damage in Nile tilapia (Oreochromis niloticus) infected withStreptococcus agalactiae.

On the other hand, in addition to improving the stability and bioavailability of food ingredients, nanoparticles can be used to modify the fish food physical attributes. Even small inclusions of nanomaterials can dramatically enhance the physical properties of food pellets. For example, inclusion of single-walled carbon nanotubes into trout diets results in a hard pellet that maintains its integrity in the water. This is important to reduce pollution and food wastage in aquaculture systems due to inappropriate buoyancy, poor food stability or texture of the pellets which causes significant losses inside this industry (Handy &Poxton, 1993). Thus, the development of nano-formulations has been heavily investigated in the industry nowadays. A fundamental characteristic of these systems is its suitability for different uses, such as delivery of antibiotics, vaccines, pharmaceuticals, and nutraceuticals,among others (Rather et al., 2011; Sibaja-Luis et al., 2019).

Current research has focused on the use of different types of biopolymers for use in the aquaculture sector (Alboofetileh et al., 2016;Borgogna et al., 2011; Dursun et al., 2010; Joukar et al., 2017). Alishahi et al. (2011) found that vitamin C encapsulated in chitosan-based nanoparticles raise the levels of vitamin C in the serum of rainbow trout (O. mykiss), when incorporated in the feed, increasing also the innate immune response, evidenced by the levels of lysozyme and hemolytic serum complement activities, compared to vitamin C and chitosan control groups.

Recently, Abd El-Naby et al. (2019), reported that dietary supplementation with chitosan nanoparticles can improve both feed utilization and growth of Nile tilapia (O. niloticus). These authors argue that the activity of enzymes such as lipase and amylase were stimulated by the inclusion of chitosan particles. In addition, it was found that the use of these nano particles can not only inhibit the growth of bacteria, both aerobic and anaerobic, but can also strengthen the innate immunity system. Additionally, Naiel et al. (2020), have reported that the mixture of vitamin C with chitosan nanoparticles shows an immuno-modulating effect against the toxicity produced by exposure to the pesticide imidacloprid. They also point out that with the supplementation of this mixture, there is an improvement of both the growth and the use of the food under the presence of pesticides in the water. In addition, they point out that the inclusion of chitosan nanoparticles and vitamin C administered through food not only have a positive effect on the anti-oxidative state and non-specific immunity, but may also have other positive health effects, which are re flected in the structure of hepatocytes and the general health status ofO. niloticusexposed to sub-lethal concentrations of imidacloprid. More recently, in a similar study,Ismael et al. (2021) report that supplementation with dietary zeolites,alone or in combination with chitosan nanoparticles, can also mitigate the effects of toxicity from exposure to imidacloprid. On the other hand,Abd El-Naby et al. (2020), also point out that the combination of chitosan nanoparticles with thymol can also have a marked positive effect on the growth and utilization of food inO. niloticus, indicating that not only the enzymatic activity of lipases, catalases and proteases are seen increased, but also the length of the intestinal villus is favored. Nevertheless, applications of nanomaterials, as nutraceutical in aquaculture(shell fish and fish), linked to added value products, stress reduction, and health management, are currently being considered at early stage,although the use of nutraceuticals remains low because of its high cost(Ogunkalu, 2019).

7.Seafood processing

Nanotechnology can be used in the production of aquaculture species as well as in marketing of seafood, particularly because of the requirement to extend product shelf-life. Research efforts in the food packaging sector have been intensified by the use of nanomaterials for being able to provide new properties, including oxygen depletion, reducing enzyme activity and product degradation, as well as antimicrobial and antifungal activities, detection of pathogens and toxins; and therefore,improving stability of the products (Jiang et al., 2015; Kumar et al.,2020; Kuswandi, 2016; Mihindukulasuriya & Lim 2014; Reig et al.,2014; Rhim et al., 2013; Sibaja-Luis et al., 2019; Siegrist et al., 2008).

A key goal of the food industry is to extend the product shelf life, in order to preserve not only the freshness, but also the food quality.Currently, nanotechnology can generate many advances applied to food processing divisions, directed to increase product shelf life by preventing gas flow across the packaging, but also give information about possible spoilt components (Nickols-Richardson & Piehowski, 2008).Nanostructures like nanoemulsion, nano fibers, and nanoparticles can be used to slow down the dacay in quality, thus keeping the color and flavor of the product (Chellaram et al., 2014; Ozogul et al., 2017).

On the other hand, there are many reports about the use of essential oils encapsulated in diverse nanostructures, including cyclic oligosaccharides (Abarca et al., 2016; Ciobanu et al., 2012; Hill et al., 2013;Siqueira-Lima et al., 2014), nanotubes (Kim et al., 2016; Lee & Park,2015), polymeric nanoparticles (Christofoli et al., 2015; De Oliveira et al., 2014; Liakos et al., 2016), solid lipid nanoparticles (Cortes-Rojas et al., 2014; Feng, 2012; Lai et al., 2006; Moghimipour et al., 2013), zein nanoparticles (Parris et al., 2005; Wu et al., 2012; Zhang et al., 2014; da Rosa et al., 2015), and biodegradable nanoparticles (Chifiriuc et al.,2017; Pavela et al., 2017; Sotelo-Boyas et al., 2017a,b), among others.

Furthermore, nanoparticles impregnated ice can be used for diverse food packaging applications. For example, silver nanoparticles, extracted from banana midrib and integrated into nano-ice, have been reported to reduce the microbial load on the flathead grey mullet (Mugil cephalus) surface, even inhibiting the growth of Acinetobacter (Daniel et al., 2016). In the field of seafood preservation, silver nanoparticles produced by organic methods are being focused more than the use of chemical synthesis (Huang et al., 2018). In addition, some animals, such as oysters, prawns, and fishes, have also been used for the nanoparticle’s synthesis. Those organisms also possess abundant resources of bioactive compounds, such as minerals, oils, proteins, lipids, flavonoids, vitamins,polyphenols, fibers, polysaccharides (fucoidan, laminaran and alginate),terpenoids, and carotenoids; all of them with many possible ethnobotanical functions (Kushnerova et al., 2010; Hussain et al., 2019).

7.1.Nano films

In the field of conservation and packaging techniques to ful fill food security, nanotechnology is being applied in seafood in the process of preservation to delay microbial and enzymatic spoilage. Products using nanomaterials with antimicrobial activity are becoming very popular,such as packaging material incorporating silver nanoparticles (Vasile,2018; Hussain et al., 2019). Nanocomposites films are incorporated into foods along with antimicrobial films and edible coating techniques.Nanocomposites films are derived from natural biopolymers, including lipid, protein, and polysaccharides. As a result of their environmental-friendly, anti-carcinogenic nature, and edibility; these substitutes packaging materials are increasingly adopted as replacement of plastics produced by petrochemical sources (Dursun et al., 2010;Ogunkalu, 2019). Different forms of chitosan nanoparticles possessing antimicrobial properties has been investigated (O’Callaghan & Kerry,2016). For example, nanocomposite films produced with chitosan nanoparticles and gelatin, with the addition of oregano essential oil,show high antimicrobial activity, including against the four most common test food pathogens (E. coli,Salmonella enteritidis,S. aureus, andListeria monocytogenes) (Hosseini et al., 2016; Hussain et al., 2019).

An emerging cumulus of information points out to chitosan as a promising edible coating material for sea-products, ideal to extend shelf life and improve the microbiological quality (Mohan et al., 2012). Chitosan is considered an efficient antimicrobial agent because of the poly cationic form (Suptijah et al., 2008). Furthermore, chitosan nanoparticles present extraordinary physiochemical properties, including bioactivity (Yang et al., 2010). Many reports show the addition of nanoparticles in bio-nanocomposite films, made with chitosan nanoparticles and gelatin which show improved barrier properties (Hosseini et al., 2015). Moreover, it was verified that nano-chitosan is a more effective antibacterial agent, compared to coating chitosan applied on silver carp fillets (Hypophthalmichthys molitrix). In Indonesia, using chitosan as a conservation agent for sea-products has been intensively studied, emphasizing in pond raised species including Nile tilapia(Oreochromissp.) (Tapilatu et al., 2016), and cat fish (Pangasiusypopthalmus) (Suptijah et al., 2008). Moreover, chitosan applications in tropical marine fishes have been reported, mainly on pretreated products, such as the salted Indian scads (Decapterussp.) (Swastawati et al., 2008; Hussain et al., 2019).

Carbon nanotubes, fullerene, graphene and graphene oxide also show very good antimicrobial properties, exerting physical damage through the damage of the cell wall and membrane as well as chemical damage through phospholipid oxidation through the production of reactive oxygen species (Azizi-Lalabadi et al., 2020). These nanomaterials could have huge potential for development of new nanocomposite materials for the packaging industry of seafood.

7.2.Nanoemulsions

Due the extremely small droplet size (<100 nm), nano-emulsions present outstanding physicochemical properties and stability (McClements, 2011; Otoni et al., 2016; Solans et al., 2005). These dimensions allow higher surface area per unit of mass, therefore improving the activity of lipophilic solutions (McClements & Rao, 2011).Nano-emulsions represent the new frontiers for the production of edible films. In order to increase water dispersion and prevent degradation of essentials oils, alginate films with essentials oil-loaded nano-emulsions have been developed (Acevedo-Fani et al., 2015). Nano-emulsion made with essentials oil, coupled with the antibacterial property of manufactured films, and thyme essentials oil, proven to inhibitE. coligrowth,as well as, the antimicrobial activity of an edible composite film,fabricated by nano-emulsified cinnamaldehyde, have been reported(Otoni et al., 2014; Hussain et al., 2019).

7.3.Nanoliposomes

Currently, essentials oils have been established their superior and enhanced antimicrobial capacities of surfactant nano-metric micelles.Nano-liposomes made with essential oils are capable to be released gradually, therefore improving the antibacterial properties of the film.For example, Wu et al. (2015b) develop cinnamon essential oil nano-liposomes, incorporated into gelatin films, which slowed the release and enhanced the antimicrobial activity. Moreover, a high antimicrobial activity is produced by the encapsulation of carvacrol and eugenol into nano-metric surfactant micelles (Gaysinsky et al., 2005).An exceptionally steady nano-liposomes resulted from the encapsulation of orange essential oil aided by soy lecithin and rapeseed, which were further incorporated into starch films of caseinate (Jimenez et al., 2014).Valencia-Sullca et al. (2016) have shown the ability of lecithin nano-liposomes for encapsulating essential oils. Furthermore, the use of eugenol in nano-liposomes of lecithin allow the films to retain about 40–50% of the incorporated eugenol, compared to only 1–2% when this compound was incorporated by a direct route of emulsification (Hussain et al., 2019).

8.Nanotechnology risk assessment and governance

Currently, the potential toxicity of nanoparticles in biological system is becoming a public concern. Nanomaterials may constitute a new source of pollutants to the environment, and research is being focused on the potential negative impact that they could produce (Moore, 2006;Shah & Mraz, 2019). Owing to its extremely small size, nanoparticles can penetrate through the cell membranes and cause genotoxicity. The intrinsic chemical reactivity of nanomaterials results in higher production of reactive oxygen species and free radicals; and its production is one of the main toxicity mechanisms of nanoparticles. This may produce not only inflammation and oxidative stress, but also damage to proteins and DNA. It has been demonstrated the nanomaterials potential to produce DNA mutation and major structural damage to mitochondria,that could even result in cell death (Majumder & Dash, 2017; Meghani et al., 2020; Vicari et al., 2018).

Many studies have reported the toxic effects of nanomaterials for aquatic organisms (Asharani et al., 2008; Griffitt et al., 2008; Matranga& Corsi, 2012; Garcia-Negrete et al., 2013; Canesi et al., 2015; Vignardi et al., 2015; Swain et al., 2016; Canesi et al., 2017; Sendra et al., 2017a;b; c; 2018a; b; 2019; Aouini et al., 2018; Volland et al., 2018; Naguib et al., 2020; Sayed et al., 2020). Nanotoxicology studies have been conducted to clarify not only regulatory aspects and bio-distribution of these components, but also to evaluate, at molecular levels, their potential risks to the environment (Bello & Leong, 2017). A sustainable approach of the use of nanotechnology into the fisheries and aquaculture industries will require more studies of those issues,including the understanding of how nanomaterials can accumulate and if they could become toxic to aquatic organism or humans (Skjolding et al., 2016; Sibaja-Luis et al., 2019). More public engagement will also be crucial to preserve the confidence in nanotechnology, especially with respect to food and environment safety.

An important question remains about the public opinion, and whether the consumers are agreeing to eat fish that may contain nanoparticles. It seems that public perception for nanotechnology is very different from the genetically modified organisms (GMO), being mostly favorable, partly attributed to the efforts made by this industry to inform the general public about the development of nanomaterials from its earliest stages (Anderson et al., 2005; Handy, 2012, pp. 1–29; Handy &Shaw, 2007; He et al., 2019; Mukherjee et al., 2019). Also, more risk analyses about potential long-term repercussions of engineer nanomaterials in human food need to be made. In the case of the aquaculture sector, the main exposure risk would link to the edible parts of the fish,like muscle. So far, data show that metal nanoparticles levels in fish tissues, from diets carry mg kg−1amounts of those nanoparticles, are in the order of ng g−1or lower (Handy et al., 2011; Khosravi-Katuli et al.,2017; Ramsden et al., 2009; Shaw & Handy, 2011). Thus, possible human health risks are likely to be associated with the long-term effects produced by the consumption of fishes that may content ng or lower quantities of nanomaterials. However, this kind of concerns are not new.Tolerable risk from persistent chemicals in edible fish, like mercury or pesticides, is regulated in the legislation on allowable levels of pollutants in aquaculture (Berntssen et al., 2010). The same model can be considered for nanomaterials. Moreover, it would be prudent to do additional studies about the public acceptability of nanomaterials in edible seafood products. Thus, more effort needs to be made to accomplish public engagement, in order to explain the current uses of nanotechnology by this industry, as well as the benefits and possible risks to the consumers (Handy, 2012, pp. 1–29).

Such concerns should not prevent us from trying to develop nanotechnology in the aquaculture sector. A careful monitoring linked to controlled use, can aid in the efforts to increase benefits and decrease risks (Ashraf et al., 2011). In this regard, a guidance about safety handling is available for laboratory workers using nanomaterials for research (Handy, 2012, pp. 1–29). Nowadays, there are no standardized protocols to evaluate the effects of man-made nanomaterials in the environment; this is partly due, not only to the wide diversity of nanomaterials, but also to the complexity of their dispersion dynamics in the environment. Thus, estimates of environmental levels are mostly derived from conceptual models of nanoparticle release. A considerable amount of the available information about the behavior and fate of nanomaterials comes from studies of freshwater ecosystems (Handy et al., 2008; Ju-Nam & Lead, 2008; Klaine et al., 2008), but also from marine environments (Bundschuh et al., 2018; Canesi & Corsi, 2016;Selck et al., 2016). From those models, the concentration levels of man-made nanomaterials in surface waters were estimated in the range of ng L−1or lower (Boxall et al., 2007; Bundschuh et al., 2018; Gottschalk et al., 2009; Metreveli et al., 2016; Nowack & Bucheli, 2007). For example, recent predictions for freshwater CeO2-nanomaterials range from 1 pg/L (2017) to a few hundred ng/L (2050). In comparison with CeO2, SiO2-nanomaterials estimates are nearly one thousand times higher, while for silver-nanomaterials ten times lower. For most of the environmental niches, nanomaterials represent relatively low risk;nevertheless, organisms that live near nanomaterial “sources”, such as waste treatment installations or production plant outfalls, could be at higher risk (Giese et al., 2018). These are only predictions and the fate and behavior of manufactured nanomaterials in important ecosystems,like the oceans, are currently not well understood. Nevertheless, Handy(2012), as well as Shah & Mraz (2019), gave us very relevant information, not only about the potential eco-toxicity, behavior and fate of man-made nanomaterials in marine environments, but also about possible schemes of surveillance and monitoring (Abdolahpur et al.,2019; Baalousha et al., 2016; Cerrillo et al., 2017; Sun et al., 2016).

The risks linked to nanomaterials, as with any new substance, should be balanced in relation to the potential benefits (Owen & Handy, 2007).The assessment of risks, benefits and ethical issues depend on several factors, not only related with the composition of nanomaterials, but also with the specific area of application, methods of deployment, and final goals. During the past few decades, a lot of effort has been centered into legislation, which has been widely reviewed (Jain et al., 2018; Kaphle et al., 2018; Wacker et al., 2016), concluding that experimental protocols should be established to help determine the possible effects for a given material prior to its application in agriculture, food and environment, in order to generate regulatory guidelines that can harness the full potential of nanotechnology.

However, no standard regulatory laws related to the use of nanotechnology in food and agricultural sector have been implemented so far. Thus, effective policies and guidelines are needed for the safer usage of nanoparticles in the industry. Due to these limitations, the actual legislation remains at the initial stage of development, covering only general approaches related to nanomaterials and nanotechnology.Nevertheless, a worldwide harmonized regulation for man-made nanomaterials is still lacking. For products not included in the GHS (Globally Harmonized System of Classification and Labelling of Chemicals of the United Nations) classification and labelling requirements, information for consumers, through declaration statements, does not exist. The same situation applied for the management of nano-waste (Karlaganis et al.,2019).

For example, inorganic oxide metals such as titanium dioxide(E171), silicon dioxide (E551), and magnesium oxide (E530) are allowed by the Food and Drug Administration (FDA) for direct human consumption. However, recently, and based on concerns about genotoxicity, the European Food Safety Authority (EFSA) has banned the use of titanium dioxide (E171) as a food additive (EFSA et al., 2021a). On the other hand, zinc oxide, iron oxide, and copper oxide now have been categorized under the GRAS (generally recognized as safe) status by the FDA as nutritional dietary supplement for animal feeds. To this last group, we should add copper oxide and di-copper oxide, which have been authorized by the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), establishing that it does not pose any risk for the health of consumers (He et al., 2019). The highly limited regulation regarding nano food, is due, in part, to the complexity of nanomaterials and by the case-by-case legislating procedures (SCENIHR,2012a; b; He et al., 2019) (Table 1). Moreover, another factor contributing to the lack of knowledge is due to the different levels of toxicity,effects and risks associated with different categories of nanomaterials(Deng et al., 2018).

Table 1Key regulation and legislation introduced by Food and Drug Administration(FDA, USA), Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), World Health Organization (WHO), European Food Safety Authority (EFSA), and Organization for Economic Co-operation and Development (OECD), related to nanotechnology and nanomaterials.

The FDA (USA) and the SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks, EU) are the two main institutions devoted to regulation and legislation on food nanotechnology. Regulations of the EU accentuate that food ingredients containing nanomaterials should undergo safety assessment in order to assure the safety for human consumption (Tinkle et al., 2014). Furthermore, nanofood or food ingredients are fully covered by the European Union Novel Foods Regulation (EC 258–97), and the REACH (Registration, Evaluation,Authorization and Restriction of Chemicals), as the main regulation instrument for EU, and the most active agency related to the legislation of nanotechnology in food industry, followed by the FDA. The EU is the most active geographical area in the implementation of norms and regulations in relation to the control of nanomaterials, mainly regarding their inclusion as a food additive. An example is the EFSA Scientific Network of Risk Assessment of Nanotechnologies in Food and Feed which celebrates in 2020 its 10th anniversary and seeks to establish new guidelines for the regulation and risk assessment of nanomaterial in agricultural/food/feed products (EFSA, 2021a). On the other hand,China and Japan, main actors in nanotechnology, need to develop regulations in the use and disposal of nanomaterials (Brien & Cummins,2010; Nile et al., 2020). However, recently (2017) Taiwan FDA introduced new regulations related to safety assessment and pre-market approval for food packaging nanomaterials (Chemical Watch, 2017).

Moreover, the Organization for Economic Co-operation and Development (OECD) stablished in 2006 the “Program on Manufactured Nanomaterials” and the “Test Guidelines Program” in order to generate the networking and multidisciplinary collaboration to promote the development and application of nanomaterials for advanced manufacturing. To further develop this goal, the OECD has launched in 2020 a new 3-year project (NANOMET) funded by the EU. Additionally,a working group of the GHS Subcommittee of the United Nations (UN)contemplates the use of the GHS criteria to man-made nanomaterials.The UN Strategic Approach to International Chemicals Management(SAICM) is the worldwide forum for discussing nano-safety issues. The SAICM presented a nano-specific resolution and integrated new activities related to nanomaterials and nanotechnologies on its Global Plan of Action (Karlaganis et al., 2019).

Different geographical zones, for example in the EU, Switzerland,Thailand, and USA, are implementing nano-regulations in compliance with the laws of the World Trade Organization (WTO). It is very important that the main regulatory objective of protecting consumers and the environment is maintained. Moreover, the legislation must not serve as a measure of protectionist to benefit domestic industries (Karlaganis et al., 2019).

While research about the safety of nanomaterials needs further development in order to guide the regulations for the use and disposal of nanomaterials, the efforts must be focused on research related, not only to the methodology for identification and characterization of nanomaterials, but also about assessment the long-term risk for humans and the environment. These tasks must be assumed by the stakeholders, in order to advance in the various issues. Additionally, the public engagement will be fundamental in order to ensure a transparent and constructive discussion (Chena & Yadab, 2011).

The potential benefits for the fisheries and aquaculture sectors are significant, and, so far, the toxicological data suggest that nanomaterials are less hazardous comparing with other chemicals already used by these industries. Furthermore, the foreseen health hazard to workers using nanotechnology products in fisheries and aquaculture seems to be within acceptable limits. It is expected that these workers will be most likely exposed to nanomaterials in commercial products, rather than raw materials containing free particles. Therefore, in terms of nanomaterial exposure, the occupational health and safety risks for most of the personal of those industries seems to be low or similar to members of the general public, given that manufactured nanomaterials are currently available in different forms of commercial products (Handy, 2012, pp.1–29). WHO presented a Guidelines on Protecting Workers from Potential Risks of Manufactured Nanomaterials, which include a list of suggested occupational exposure limits (WHO, 2017).

The governance for nanotechnology applications in aquaculture, as well as in others agriculture sectors, should be discussed in terms not only of intellectual property and technology transfer models, but also about sustained financial investment in research and development.Moreover, more effort must be made to promote the incorporation and exchange of the technology and among developing countries. Intrinsically, nanotechnology has and will need multidisciplinary involvement and collaboration between the different key players, such as researchers,industry, government and the general public (Chena & Yadab, 2011).

Since the last decade, several countries, particularly India, Brazil and South Africa, have already been widely investing on research and development of nanotechnological applications related to different agriculture sectors and food systems (Gruere et al., 2011). In this context, the synergistic combination between public-private sector partnerships and developed-developing countries collaborations could be useful in order to achieve the main goals of the aquaculture sector,and, ultimately, resulting in mutual and global benefits (Chena & Yadab,2011).

9.Conclusions

Currently, various nanotechnological applications have been implemented to improve the aquaculture industry, which could play an important role in the development and sustainability of this industry in the future. Nowadays, there are many potential applications for nanomaterials in the fisheries and aquaculture industry. Some of the most promising areas in this field are applications related to fish health management, nanoscale ingredient incorporation, use of nanotechnology in aquaculture feeds and food packaging, as well as applications linked to value-added products, stress reduction and health management. Currently, most of these applications are in an early stage, and high cost is considered the main limiting factor for their wide implementation.

Sustainable development of nanotechnology in the fisheries and aquaculture industries will require a comprehensive assessment of its potential negative impacts; therefore, a careful analysis of the life cycle and shelf life of new nanomaterials, combined with an assessment of potential health and environmental risks, including exposure, release and deposition, must be performed. However, such concerns should not prevent us from trying to implement nanotechnological applications in the aquaculture sector, which should be linked to careful monitoring and controlled use, thus favoring efforts to minimize risks and maximize benefits.CRediT authorship contribution statement

Carlos Fajardo: Conceptualization, sampling, otolith characterization, molecular analysis, Formal analysis, Writing – original draft.Gonzalo Martinez-Rodriguez: Conceptualization, Formal analysis,Writing – review & editing. Julian Blasco: Formal analysis, Writing –review & editing. Juan Miguel Mancera: Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing. Bolaji Thomas: Formal analysis, Writing – review & editing. Marcos De Donato: Conceptualization, Formal analysis, Writing – original draft,Writing – review & editing.

Declaration of competing interest

The authors declare that there is no conflicts of interest.

Acknowledgements

The authors would like to thank the financial support to Fajardo C.by the Ministry of Universities of the Government of Spain through the European Recovery Instrument "Next Generation-UE" of the European Union, through the program: Aid for the Re-qualification of the Spanish University System for 2021-2023 under the modality Margarita Salas Grants for the Training of Young Doctors. The authors also want to thank the editors and reviewers of Aquaculture and Fisheries for all of their useful comments and suggestions to improve this manuscript.