Emerging investigator series: nanotechnology to develop novel agrochemicals: critical issues to consider in the global agricultural context

Melanie Kah*a and Rai Kookanabc
aSchool of Environment, University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand. E-mail: melanie.kah@auckland.ac.nz
bCSIRO Land & Water, Locked bag 2, Glen Osmond, SA 5064, Australia
cUniversity of Adelaide, School of Agriculture, Food and Wine, Locked bag 1, Glen Osmond 5064, Australia

Received 12th March 2020 , Accepted 21st May 2020

First published on 22nd May 2020


Research and development on potential use of nanotechnology in agriculture have intensified exponentially over the last decade. Claims of superior efficacy, lower costs, improved sustainability etc. relative to conventional practices have been made. The promises, however, are not always fully substantiated, and thus may even prove counter-productive. Considering the shifts in drivers for the development of nano-enabled solutions, regulatory and public perception and to geographical discrepancies in terms food production, we reflect on how the proposed nano-enabled solutions are likely to meet the need in the global agricultural context. The potential of nanotechnology to reduce undernourishment and food insecurity at the global scale remains largely uncertain. Nanotechnology needs to align with the unique needs of emerging economies, where the scope of improvements are large but challenges abound. Regulatory requirements under development are extremely stringent for nanoformulations as the fate and hazard of different components (i.e. active substance, co-formulants and other adjuvants) need to be considered individually as well as together, which is typically not required for conventional agrochemicals. Organic nanocarriers are particularly difficult to track in food and environment and it is not always clear how regulatory requirements may be fulfilled. From our perspective, less focus should be placed on trying to define a clear boundary between nano vs. non-nano as it may slow down the uptake of innovations that will improve agrochemicals. More work is also needed to successfully design and synthesise materials that can outperform current agrochemicals through molecular-level tuning of properties. New approaches suitable for life cycle assessments of both nano and conventional agrochemicals are needed to support comparative evaluations. Besides, a global context, a multidisciplinary/interdisciplinary approach and a collective thrust by innovators is a must for realisation of true potential of nanotechnology in food and environment sector.



Environmental significance

Improvements of our food systems are urgently needed to increase worldwide food security, reduce malnutrition, and reduce the environmental footprint of agriculture. Nanotechnology can help reduce some of the widely acknowledged inefficiencies in current agricultural practices but concerns have also been expressed about nano-enabled products creating new risks to the environment. A thorough understanding of the interactions between nano-enabled products with critical ecosystem components (including plants, pests, microbiomes, livestock) is essential. The agronomic context and geographical differences – including the economic, political and social constraints that lead to food insecurity and high environmental impact – should be integrated to support the development of viable and sustainable nano-innovations in agriculture.

Introduction

Research into the applications of nanotechnology in the agri-food sector has been very active over the last decade and research efforts in the field continue to intensify. The diversity of potential nano-enabled strategies to achieve higher productivity and sustainability in agriculture have been the focus of several literature reviews on applications for plant protection and nutrition1,2 as well as animal health3 or the design of sensors.4 The latest research developments have been presented with a focus on specific types of particles (e.g. metallic nanoparticles,5 silica,6 selenium,7 carbon nanomaterials8), different approaches (e.g. the use of biopesticides,9,10 precision agriculture,11 delivery of genetic material12) or particular sectors of agriculture (e.g. horticulture,13 aquaculture14).

The motivation behind the development of most products captured in the peer review literature can be grouped into closely related categories: (i) supporting worldwide food security (mainly by increasing productivity), (ii) increasing the efficiency of inputs (e.g. reducing the application rates of agrochemicals), and (iii) providing solutions for problems that cannot be tackled with current technology (e.g. viral diseases15 or trunk diseases16).

Here we offer a concise and critical reflection on the developments that have occurred in the field over the last decade, and how they fit in the global agricultural context. Our main aim is to share our views on what is currently lacking in terms of realising the true potential of nano-innovation in agrochemicals sector and how this can be better aligned with the global food and environmental needs. An allied objective is to draw more attention on contextual aspects that need to be considered to set realistic goals and guide impactful future research.

Shifts in the drivers for nanotechnology in agriculture

The early premise of nanotechnology was to discover novel modes of action and bring new paradigms to plant protection and plant nutrition. With a few exceptions however, most nano-enabled agrochemicals proposed up to now consists of delivery systems loaded with a molecule or releasing an active ingredient. So far the mode of action remains unchanged relative to conventional agrochemicals and improvements in efficacy can be well explained by differences in the location and/or kinetics of delivery of the active ingredient.17 The novel modes of action via nanotechnology in agrochemicals remain elusive.

In terms of novel active ingredients, a large body of literature was published around the use of inorganic nanoparticles to suppress pathogen infection through direct antimicrobial action and/or improved nutrition of the plant host, as recently reviewed in.18 Increasing crop resilience through a balanced nutrition is not new, but research on nanoparticles has stimulated investigations into the mechanisms involved (e.g. production of reactive oxygen species, release of metal species, electrostatic interactions, secondary metabolic processes18). Many of these studies do not include adequate controls and it is not always possible to establish whether the effects observed are nano-specific or not.18 Nevertheless, investigations aiming to elucidate the mechanisms involved often apply advanced methodologies (e.g. synchrotron-based methods, omics) that generate knowledge that is highly valuable beyond the field of nanotechnology and can help improve practices and develop effective solutions (nano or not) for unresolved issues. For instance, solutions are urgently needed for situations where soils are deficient in nutrients and where pests cannot be controlled, either because there is no treatment or because they have developed tolerance towards the mode of action of conventional agrochemicals.

An important rationale to conduct research on the topic is the need to increase food production to match the demands of the increasing world population. The FAO estimates that more than 820 million people suffer from hunger worldwide, while no region is exempt from the epidemic of overweight and obesity. The situation is most alarming in Africa, where the prevalence of undernourishment is about 20% of the population, reaching up to 31% in Eastern Africa.19 Some nano-enabled solutions have been shown to increase yields but impacts on hunger and food security at the global scale are largely uncertain (see the section “Not one size fits all” and “Technology vs. good practices”).

The inefficient delivery of agrochemicals to target organisms remains as one of the main environmental issues associated with intensive agriculture. Losses are highly variable according to the pedo-climatic conditions, the type of crop and practices including the mode of application. Great improvement has been made since the 1980s when it was estimated that only 0.1% of pesticides applied to crops reach their target.20 However, current losses still range between 10–75% (ref. 21 and 22) and many studies have explored how nanotechnology can support the design of more efficient plant protection and micronutrition strategies. While losses of pesticides have often been the focus for nano-agrochemicals, a greater focus on nitrogen and phosphate would be desirable as the excess use and losses of nutrient used in agriculture also result in serious issues including eutrophication and toxic algal bloom in many countries.

Evolution of nano-enabled agrochemicals with time

The type of nanomaterials considered for agricultural applications has evolved over the last decade. Initially, the members of the nano community considered mostly the now “classical” engineered nanoparticles for applications in agriculture (e.g., carbon nanotubes, metal oxides, nano silver).23 It is now well recognised that most engineered nanoparticles can induce effects on a plant-pest-soil system (either positive or negative) mainly depending on the engineered nanoparticle concentration.24,25 However, only a very small number of such materials appear to be promising with regards to their agronomic and economic performances (see the section below). Members of the agrochemical community have worked towards the development of controlled-release formulations for several decades now.26 The interests and approaches of these two communities are slowly converging towards the development of a new generation of more complex platforms. The 100 nm size boundary is now often exceeded, which brings regulatory difficulties to distinguish what is nano and what is not (see the section below). Novel functions are exploited through the design of more sophisticated hybrid materials designed at the nanoscale and sometimes combining organic and metallic elements (e.g. chitosan with copper18), while others are inspired by nanoparticles used in the pharmaceutical and food sector (polymer based delivery systems27). There has been a recent increased interest in natural polymers such as chitosan,28 plant-derived sugar such as zein,29 and other natural structures such as virus capsids,30 clay15 or tannic acid31 to design delivery systems. Fundamental improvements in our capacity to design and synthetize materials that can be tuned at the molecular levels are needed to realise the full potential of such platforms. Research in this area is gaining momentum and is likely to generate exciting results in the near future. We can foresee that such structures will also support the use of novel approaches to pest control e.g. RNAi.12 Whether these structures are or need to be considered as “nano” is unclear, but they will certainly play a role in the future of agriculture.

In parallel to the innovations in nano-enabled agrochemicals, biopesticides have seen a major growth, partly aided by nanotechnology. For example, there has been active research to use nanodelivery systems to formulate naturally occurring chemicals e.g. plant extract, essential oils etc.,10 which are claimed to be sustainable alternative to synthetic chemistry. Generally, biopesticides are perceived by the public as safer alternatives. However, pesticide actives have long been inspired by naturally occurring molecules, with examples including pyrethroids and neonicotinoid insecticides. A biological origin does not make a compound less hazardous than one produced through synthetic chemistry. Sophisticated nanodelivery systems add uncertainty to this assessment and they may also bring conflicting messages about how “natural” the agrochemical product is.

Shifts in perspectives and perceptions

Scientists

Early studies by environmental scientists were often driven by concerns about potential risks associated with nano-enabled products through for instance, toxicity to non-target organisms investigated in short term and high exposure tests. More studies are now also reporting on the potential environmental benefits that nanotechnology can bring to agriculture, including the reduction in agrochemicals application rates or reduced toxicity to non-target organisms.32,33 Both risks and benefits, therefore, need be considered in parallel.34

Regulators

Regulatory definitions have been proposed for engineered nanoparticles, along with difficulties associated with the capacity to provide measurements for the criteria proposed, as well as some overlaps and some contradictions.35 In its recent guidance to evaluate nanotechnologies in the food and feed chain, the European Food and Safety Authority adopted a rather inclusive definition and precautionary approach.36 For instance, the guidance covers both engineered as well as natural materials and also explicitly includes particles larger than 100 nm that could retain properties characteristics of the nanoscale. The EFSA guidance also highlighted the need to assess the safety of the individual components of nanoformulations (i.e. active substance, co-formulants and other adjuvants) as well as the safety of all components together, which is currently not a requirement for conventional formulations. Based on characterisation data published in the literature, there is growing evidence that distinguishing a nano from a conventional agrochemical cannot be based on a size criteria alone.37 The absence of clear boundaries brings regulatory challenges e.g. if a conventional agrochemical used for decades is found to contain nanoparticles, it should be assessed through robust and applicable approaches.38 In Europe and other parts of the world, it is important to recognise the increased scrutiny around the persistence of agrochemicals as a cut off criteria for placement on the market. This means that highly persistent type of nanomaterials (carbon nanotubes, metal and metalloids) are likely to face more regulatory hurdles relative to organic molecules that can be degraded.

Public

In many countries including in Europe, Australasia and India, organic production (i.e. with no synthetic amendment) is gaining popularity and consumers' preferences in buying food products is expected to change in the future. Many nano-enabled agrochemicals combine sophisticated synthesis processes with polymers, structure and/or active ingredients from natural origin. It is difficult to predict how the public will react.39 For instance, copper is an important fungicide used in organic farming that led to significant soil contamination.40 Would nano-forms of Cu that allow a reduction in application rates be accepted or even allowed in organic practices? Many social factors will determine whether growers and consumers are ready to adopt nanotechnology in food production. Developers should thus carefully consider whether their products are congruent with consumer preferences and the needs of specific groups of growers e.g. in developing countries vs. hydroponics. This could be achieved by establishing stronger links with professional associations and collaborations with social scientists.

The need to track agrochemicals after application

Despite decades of intensive research, our understanding and control of the processes driving the fate of conventional agrochemicals in the field is still limited; the uncertainty associated with nano-enabled agrochemicals is even greater. Further research is required towards a better understanding of the dynamic processes occurring in agro systems. It is important to establish how particles interact with plants, soil and microorganisms, and how these processes may differ between the laboratory and the field, within a field, and from one field to another depending on the plant, soil properties and water regime. These questions are complex and require tracking nanoparticles in the environment, which is not a trivial task.

There have been great progresses to develop detection, characterisation and labelling approaches to investigate the environmental behaviour and toxicity of metal oxide nanoparticles.41 Most of the methods proposed are however poorly applicable to organic nanoparticles that are now often considered for applications in agriculture. Suitable analytical approaches need to be developed to support the development of performant delivery approaches for agrochemicals, as well as to achieve satisfactory regulatory approval framework. Organic nanocarriers are particularly difficult to track within organic matrices (e.g. soil or leaf material) due to the lack of contrast, and indirect methods seem to be the most promising at the moment.27 Similar analytical issues are faced when tracking polymers and nanoplastics in environmental matrices42 and food matrices43 and stronger linkages with current research in these fields would be beneficial.

Critical evaluation of product performance

The true potential of nanotechnology to improve agrochemicals is currently difficult to evaluate.17 Most results are obtained under laboratory conditions that do not reflect the reality in the field. The peer-review literature tends to emphasise cases where large differences between nano and non-nano solutions are recorded (e.g. greater performances or greater risks), whereas cases where little or no differences are observed may not be reported. There are many reasons why researchers may want to maximise impact by reporting the most remarkable findings but selective reporting also generates a biased insight on the true applicability of nano-solutions across a variety of situations (e.g. different active substances, soils, or environmental conditions). The review by Zuverza-Mena et al.44 on the effects of nanoparticles on plants included a useful figure showing the few “no effect” study published, together with the many cases where conflicting results were reported, highlighting the variability in response observed.

It is also essential that the performances of nano-enabled products are critically benchmarked against existing products, including under field conditions, and that negative/neutral results are reported to support an objective assessment of new risks and benefits.45 Doses are typically compared in terms of mass of active ingredient, but there may be cases where comparisons based on particle number or surface area may be more suitable. The consideration of adequate controls is also essential. These should include untreated controls and positive controls with the unformulated active ingredients(s), commercial product(s) as well as treatments that account for confounding factors contributing to the desired outcome e.g. P and Ca from nano-hydroxyapatite in a nanocomposite can improve yield and should be considered. Additional investigations with the individual components of the nano-products may also be needed to distinguish and understand the processes involved.

As the most promising products develop, they are also likely to be filed as patents and kept under confidentiality for future commercial development. Data from websites and patents indicate that performances is not always measured in terms of yield, but also ease of use (e.g. combining incompatible pesticide and fertiliser in a single application to crop).1 Indirect benefits of nanotechnology should be carefully considered. For instance, energy and money savings may be achieved if the number of spray events is reduced or if the agricultural machinery becomes lighter and more performant. Using nanotechnology to recover nutrients from e.g. wastewater can help reduce the environmental cost associated with the production and use of fertilisers. The cost of the nanomaterial production also needs to be factored in, ideally considering energy, chemical, water as well as social cost. Food systems are inherently complex and there are obstacles to the application of holistic approaches such as life cycle analyses.46 We can hope that tools will soon develop to help identify global benefits to society and promote the adoption of the nano-enabled solutions by users and governments (that can promote implementation through subsidies).

Not one size fits all

Increasing food production to match the needs of the increasing world population is often mentioned as one of the key drivers to apply nanotechnology in the food production sector. The current global food production is probably sufficient to feed more than 10 billion people47 and many factors other than production are responsible for the prevalence of undernourishment and food insecurity. These include economic factors, conflicts, climate variability, and inherent inefficiencies in the food distribution and use chains.19 Further considerations on how nanotechnology could improve crop resilience to e.g. drought,48 and more generally improve efficiency all along the food chain supply are thus valuable.49

Many nano-enabled products presented so far target crops that are already close to their maximum yield potential in intensive agricultural systems. The green revolution of last century allowed a great improvement in productivity. For instance, the world average yield for cereals increased by almost three-fold in the last 50 years (from 1.4 tons per ha to 4.0 tons per ha (ref. 50)). Yields increased mainly in developed countries and in some developing countries (e.g. India) where agriculture has become highly technical and optimised to reach up to 80% of the yield potential. In less developed countries (especially in Africa), yields have hardly improved since the 1970's.1 More work is thus urgently needed to tackle the challenges faced in regions with high food demand and where productivity remains low and uncertain. This requires a clear identifications of key productivity constraints in such regions and innovation need to be well-aligned to these. Specific initiatives are needed to facilitate targeted nano-technological solutions for such regions. The advancements in nanotechnology sector need to be cognisant of the unique needs of emerging economies, such as small holdings, low purchasing power of growers, subsistence agriculture, poor industrial base, low literacy and educational status, weak complementary/supporting technology, emerging regulatory environment, etc. The technological advancement aimed at the developed world rarely transfers to emerging economies.

Most nano-enabled technologies proposed so far seem to fit best in the context of developed countries that have already achieved high levels of productivity. In this space, the most promising directions may be to look at tackling problems that cannot be well tackled with current technology, high value crops (e.g. horticulture) and/or approach novel paradigm to grow food (e.g. vertical growth systems). Benefits in the shorter term are likely to be mainly associated with a reduction in inputs and/or a facilitation of in-farm interventions rather than improvement in the global food security.

Technology vs. good practices

Good practices can significantly reduce agricultural inputs and food waste. A study recently considering more than 900 farms located in France suggests that a large reduction in pesticide use (42%) is already accessible to farmers without impacting productivity or profitability.51 Farmers education is essential to achieve best practices and harness the whole potential of existing and future technologies. There are many countries where corruption, illicit practices and the lack of education are responsible for crop losses and contamination with agrochemicals. For instance, a survey in Ghana indicates that over 44% of the farmers use more pesticide than the doses recommended on the label, and 20–40% have never used personal protective equipment.52 Cross border trafficking of poor quality, spurious and sometimes unidentified agrochemicals (with labels in a foreign language) have been recognised to be a problem, e.g. in Southeast Asia (Cambodia, Laos, Myanmar) and West Africa.53 Agricultural systems that rely too heavily on technological development may also become less resilient. For instance, the great scientific discoveries that led to the development of genetically modified organisms in the 1990's have also generated a number of significant drawbacks that affect particularly small and vulnerable farmers and include rising seed costs, debts and increased dependence on multinational seed companies.54,55

Most studies on the performances of nano-enabled agrochemicals are conducted under ideal laboratory conditions17 and it is difficult to assess efficacy in the context of variable farming practices and field heterogeneity (e.g. slope, soil type, climate events). Relative to the pharmaceutical and food processing industry, agriculture is a small margin market. Nano-enabled solutions for food production need to be economically competitive with currently used products, improving both the productivity and profitability, especially in the current context where the cost burden of agrochemicals tends to increase.56 More critical analyses considering the users' perspectives are needed57 as nano-enabled solutions representing a clear advantage for the farmers are the most likely to be commercial success.

Nano or not nano?

There are some disagreements among scientists, regulators and inventors on whether some technologies are truly ‘nano’ or not. Academic research has become very competitive and researchers can see a direct benefit from using the “nano” prefix, which suggests innovative and disruptive aspects, and may facilitate funding or publication process. However, many nano-products can be seen as the result of continuous developments in formulation technologies. A good example is the term nanoemulsion used to designate emulsions with a droplet size that can overlap and often exceed that of microemulsions, which are on the market for several decades.58 In this context, nano-enabled innovations should not be treated separately nor pursued independently from non-nano innovations. For instance, more collaborations between nano communities with those that have worked on the development of slow release formulations up to now would be beneficial. Very small particles are likely to release their cargo very fast under field conditions and they may not be ideal for sustained release over time. Nanotechnology can help designing larger particles that are nanostructured. The theories, synthesis and characterisation methods developed in the nano-community can be applied to increase understanding and performances, and to advance technology generally. Conventional and nano advancements in agrotechnology clearly overlap and we would benefit from working at these intersections and building synergies. The “nano” label then becomes obsolete.

Conclusions and recommendations

Improvements of our food systems are urgently needed to increase worldwide food security, reduce malnutrition, and reduce the environmental footprint of agriculture. The gains in productivity and in efficiency brought by novel technological developments such as those associated with nanotechnology are not always competitive relative to the gains achieved by improvements in existing agronomic practices. Nano-enabled products presented so far were mainly developed to suit regions with a positive food balance, and where productivity and food wastage are high. In this context, nano-enabled tools are unlikely to replace existing tools, but they can clearly enhance and complement them and should be considered together.

The potential applications and impacts of nanotechnology in agriculture are highly context-dependent and generic solutions are unlikely to solve the current challenges faced globally. More nano-solutions should be developed with a specific objective and context in mind (i) to address the challenges currently faced by growers, (ii) to ensure cost competitivity in an industry with small profit margins, and (iii) to pro-actively address the risks of regulatory and public rejection. There is a need to align the innovations in nano-enabled agrochemicals with the specific yield constraints and needs of the regions marred with low productivities and with greater margin for improvement. Specific initiatives are needed to facilitate targeted nano-technological solutions for such regions.

Products aiming to achieve higher yields should be tested under relevant field conditions, in particular if they aim at improving production in regions where practices are poor, and where pedo-climatic conditions are unfavourable and variable. When the aim is to reduce reliance on currently used agrochemicals, both technological development and improvement of agronomic practices should be considered concurrently. Nanotechnology can benefit agriculture both directly (e.g. increasing yields, reducing the use of chemicals) as well as indirectly (e.g. reduced energy demand at various step of the food production). Assessing the potential negative impacts on ecosystems and human health is also essential while considering the whole life cycle of the technological development. Current high concerns about sustainability and food security are fully justified. More strategic and interdisciplinary research is thus urgently needed to support technological innovation that will contribute to achieving more economically and environmentally sustainable food production at the global scale.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We acknowledge the support from IUPAC via projects on nano-enabled pesticides.

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