Making food systems more resilient to food safety risks by including artificial intelligence, big data, and internet of things into food safety early warning and emerging risk identification tools.

To enhance the resilience of food systems to food safety risks, it is vitally important for national authorities and international organizations to be able to identify emerging food safety risks and to provide early warning signals in a timely manner. This review provides an overview of existing and experimental applications of artificial intelligence (AI), big data, and internet of things as part of early warning and emerging risk identification tools and methods in the food safety domain. There is an ongoing rapid development of systems fed by numerous, real-time, and diverse data with the aim of early warning and identification of emerging food safety risks. The suitability of big data and AI to support such systems is illustrated by two cases in which climate change drives the emergence of risks, namely, harmful algal blooms affecting seafood and fungal growth and mycotoxin formation in crops. Automation and machine learning are crucial for the development of future real-time food safety risk early warning systems. Although these developments increase the feasibility and effectiveness of prospective early warning and emerging risk identification tools, their implementation may prove challenging, particularly for low- and middle-income countries due to low connectivity and data availability. It is advocated to overcome these challenges by improving the capability and capacity of national authorities, as well as by enhancing their collaboration with the private sector and international organizations.

Comparative safety assessment of genetically modified crops: focus on equivalence with reference varieties could contribute to more efficient and effective field trials.

The initial compositional analysis of plants plays an important role within the internationally harmonized comparative safety assessment approach for genetically modified plants. Current EFSA guidance prescribes two types of comparison, namely difference tests with regard to a conventional comparator or control, and equivalence tests with regard to a collection of commercial reference varieties. The experience gained so far shows that most of the statistically significant differences between the test and control can be discounted based on the fact that they are still within equivalence limits of reference varieties with a presumed history of safe use. Inclusion of a test variety and reference varieties into field trial design, and of the statistical equivalence test would already suffice for the purpose of finding relevant parameters that warrant further assessment, hence both the inclusion of a conventional counterpart and the performance of difference testing can be omitted. This would also allow for the inclusion of safety testing regimes into plant variety testing VCU (value for cultivation and use) or other, independent variety trials.

Occurrence and Nature of Off-Target Modifications by CRISPR-Cas Genome Editing in Plants.

CRISPR-Cas-based genome editing allows for precise and targeted genetic modification of plants. Nevertheless, unintended off-target edits can arise that might confer risks when present in gene-edited food crops. Through an extensive literature review we gathered information on CRISPR-Cas off-target edits in plants. Most observed off-target changes were small insertions or deletions (1-22 bp) or nucleotide substitutions, and large deletions (>100 bp) were rare. One study detected the insertion of vector-derived DNA sequences, which is important considering the risk assessment of gene-edited plants. Off-target sites had few mismatches (1-3 nt) with the target sequence and were mainly located in protein-coding regions, often in target gene homologues. Off-targets edits were predominantly detected via biased analysis of predicted off-target sites instead of unbiased genome-wide analysis. CRISPR-Cas-edited plants showed lower off-target mutation frequencies than conventionally bred plants. This Review can aid discussions on the relevance of evaluating off-target modifications for risk assessment of CRISPR-Cas-edited plants.

Biotechnology and Biosafety Policy at OECD: Future Trends.

The OECD Council Recommendation on Recombinant DNA Safety Considerations is a legal instrument which has been in force since 1986. It outlines the safety assessment practices that countries should have in place for agricultural and environmental biotechnology. This article suggests possible updates to make it suitable for the modern era.

Application of the Safe-By-Design Concept in Crop Breeding Innovation.

The present paper proposes the application of the safe-by-design concept to crop breeding innovation with the aim to accommodate safety considerations for new agricultural food and feed products. Safe-by-design can be implemented in all stages of the innovation cycle of agricultural products, from the early stages of research and development towards the post-market stage. Our proposed application of safe-by-design can be part of "responsible research and innovation" concepts, because they share features such as risk prevention strategies and a participatory approach. Early awareness of potential safety issues can guide the development of agricultural products towards safe options, both at the process and product level, and thus may help to reduce extensive pre-market assessment studies that might otherwise be needed further downstream for regulatory product approval. Here, it is discussed how the proposed safe-by-design approach can be introduced into the development of safe food crops using emerging technologies, such as gene editing and synthetic biology, and how this may help to safeguard the safety of our food and feed supply in the light of the ongoing global innovations in agricultural crop breeding.

Food safety assessment of crops engineered with RNA interference and other methods to modulate expression of endogenous and plant pest genes.

Genetically modified crops have been grown commercially for more than two decades. Some of these crops have been modified with genetic constructs that induce gene silencing through RNA interference (RNAi). The targets for this silencing action are genes, either specific endogenous ones of the host plant or those of particular pests or pathogens infesting these plants. Recently emerging new genetic tools enable precise DNA edits with the same silencing effect and have also increased our knowledge and insights into the mechanisms of RNAi. For the assessment of the safety of foodstuffs from crops modified with RNAi, internationally harmonized principles for risk assessment of foods derived from genetically modified crops can be followed. Special considerations may apply to the newly expressed silencing RNA molecules, such as their possible uptake by consumers and interference with expression of host genes, which, however, would need to overcome many barriers. Bioinformatics tools aid the prediction of possible interference by a given RNA molecule with the expression of genes with homologous sequences in the host crop and in other organisms, or possible off-target edits in gene-edited crops. © 2020 The Author. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Regulation and safety considerations of somatic cell nuclear transfer-cloned farm animals and their offspring used for food production.

This document discusses recent developments in cloning of husbandry animals through somatic cell nuclear transfer, particularly with a view on improvements in their efficacy. Commercial developments in North and South America, Australia-New Zealand, and China are noted. The regulations and safety aspects surrounding the use of clones and their offspring for the purpose of food production are discussed. It is generally considered that foods from offspring of clones are no different than similar foods from conventional animals, yet besides safety, also ethical and animal welfare considerations come into play at the policy level. The related topic of detection and traceability of clones is discussed, which covers both molecular and documentary methods.

Gene-Edited Crops: Towards a Harmonized Safety Assessment.

Gene editing and other innovative plant breeding techniques are transforming the field of crop biotechnology. Divergent national regulatory regimes worldwide apply to crops bred with these techniques. A plea is made for international harmonization of the premarket assessment of their safety. Such harmonization has previously been achieved for genetically modified (GM) crops.

One-year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu ) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.

Developing Global Leaders for Research, Regulation, and Stewardship of Crop Protection Chemistry in the 21st Century.

To provide sufficient food and fiber to the increasing global population, the technologies associated with crop protection are growing ever more sophisticated but, at the same time, societal expectations for the safe use of crop protection chemistry tools are also increasing. The goal of this perspective is to highlight the key issues that face future leaders in crop protection, based on presentations made during a symposium titled "Developing Global Leaders for Research, Regulation and Stewardship of Crop Protection Chemistry in the 21st Century", held in conjunction with the IUPAC 13th International Congress of Pesticide Chemistry in San Francisco, CA, USA, during August 2014. The presentations highlighted the fact that leaders in crop protection must have a good basic scientific training and understand new and evolving technologies, are aware of the needs of both developed and developing countries, and have good communication skills. Concern is expressed over the apparent lack of resources to meet these needs, and ideas are put forward to remedy these deficiencies.

A holistic approach to food safety risks: Food fraud as an example.

Production of sufficient, safe and nutritious food is a global challenge faced by the actors operating in the food production chain. The performance of food-producing systems from farm to fork is directly and indirectly influenced by major changes in, for example, climate, demographics, and the economy. Many of these major trends will also drive the development of food safety risks and thus will have an effect on human health, local societies and economies. It is advocated that a holistic or system approach taking into account the influence of multiple "drivers" on food safety is followed to predict the increased likelihood of occurrence of safety incidents so as to be better prepared to prevent, mitigate and manage associated risks. The value of using a Bayesian Network (BN) modelling approach for this purpose is demonstrated in this paper using food fraud as an example. Possible links between food fraud cases retrieved from the RASFF (EU) and EMA (USA) databases and features of these cases provided by both the records themselves and additional data obtained from other sources are demonstrated. The BN model was developed from 1393 food fraud cases and 15 different data sources. With this model applied to these collected data on food fraud cases, the product categories that thus showed the highest probabilities of being fraudulent were "fish and seafood" (20.6%), "meat" (13.4%) and "fruits and vegetables" (10.4%). Features of the country of origin appeared to be important factors in identifying the possible hazards associated with a product. The model had a predictive accuracy of 91.5% for the fraud type and demonstrates how expert knowledge and data can be combined within a model to assist risk managers to better understand the factors and their interrelationships.

Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu ) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event.

The impact of altered herbicide residues in transgenic herbicide-resistant crops on standard setting for herbicide residues.

The global area covered with transgenic (genetically modified) crops has rapidly increased since their introduction in the mid-1990s. Most of these crops have been rendered herbicide resistant, for which it can be envisaged that the modification has an impact on the profile and level of herbicide residues within these crops. In this article, the four main categories of herbicide resistance, including resistance to acetolactate-synthase inhibitors, bromoxynil, glufosinate and glyphosate, are reviewed. The topics considered are the molecular mechanism underlying the herbicide resistance, the nature and levels of the residues formed and their impact on the residue definition and maximum residue limits (MRLs) defined by the Codex Alimentarius Commission and national authorities. No general conclusions can be drawn concerning the nature and level of residues, which has to be done on a case-by-case basis. International residue definitions and MRLs are still lacking for some herbicide-crop combinations, and harmonisation is therefore recommended.

Indicators of emerging hazards and risks to food safety.

There is a widely felt need to develop methods for the early identification of emerging hazards to food safety with the aim of preventing these hazards from becoming real risks and causing incidents. This paper reviews various activities and previous reports that describe methods to select indicators that can be used for the purpose of early identification of hazards. These indicators have been divided over three different environments, including (i) the environment surrounding food production, (ii) the food production chain from farm to fork, and (iii) consumers. Changes in these indicators are signals that may require follow-up action. Besides indicators that are linked to specific kinds of hazards, the indicators used for vulnerability assessment can help identifying weak spots in the food production system that are sensitive to a broader range of hazards. Based on the various indicators for emerging hazards that have thus been identified in literature, a set of generic indicators is provided that can be useful for the early identification of hazards.

GMDD: a database of GMO detection methods.

BACKGROUND: Since more than one hundred events of genetically modified organisms (GMOs) have been developed and approved for commercialization in global area, the GMO analysis methods are essential for the enforcement of GMO labelling regulations. Protein and nucleic acid-based detection techniques have been developed and utilized for GMOs identification and quantification. However, the information for harmonization and standardization of GMO analysis methods at global level is needed. RESULTS: GMO Detection method Database (GMDD) has collected almost all the previous developed and reported GMOs detection methods, which have been grouped by different strategies (screen-, gene-, construct-, and event-specific), and also provide a user-friendly search service of the detection methods by GMO event name, exogenous gene, or protein information, etc. In this database, users can obtain the sequences of exogenous integration, which will facilitate PCR primers and probes design. Also the information on endogenous genes, certified reference materials, reference molecules, and the validation status of developed methods is included in this database. Furthermore, registered users can also submit new detection methods and sequences to this database, and the newly submitted information will be released soon after being checked. CONCLUSION: GMDD contains comprehensive information of GMO detection methods. The database will make the GMOs analysis much easier.

Comparison of herbicide regimes and the associated potential environmental effects of glyphosate-resistant crops versus what they replace in Europe.

While cultivation of transgenic crops takes place in seven of the EU member states, this constitutes a relatively limited part of the total acreage planted to these crops worldwide. The only glyphosate-resistant (GR) crop grown commercially until recently has been soybean in Romania. In addition, large-scale experimental European data exist for GR sugar and fodder beets, and, to a lesser extent, GR oilseed rape. These GR crops are likely to have an impact both on the use of herbicides and on the environmental impact of the latter. From the data on these GR crops, it appears that quantities of herbicides applied to GR beets are decreased while those on GR soybean are slightly increased compared with their conventional counterparts. Depending on the parameters used for prediction or measurement of environmental impacts of GR crops, generally similar or less negative impacts were observed compared with conventional crops. Favourable environmental effects of the glyphosate-containing herbicide regimes on GR crops appear feasible, provided appropriate measures for maintaining biodiversity and prevention of volunteers and gene flow are applied.

Altered pesticide use on transgenic crops and the associated general impact from an environmental perspective.

The large-scale commercial cultivation of transgenic crops has undergone a steady increase since their introduction 10 years ago. Most of these crops bear introduced traits that are of agronomic importance, such as herbicide or insect resistance. These traits are likely to impact upon the use of pesticides on these crops, as well as the pesticide market as a whole. Organizations like USDA-ERS and NCFAP monitor the changes in crop pest management associated with the adoption of transgenic crops. As part of an IUPAC project on this topic, recent data are reviewed regarding the alterations in pesticide use that have been observed in practice. Most results indicate a decrease in the amounts of active ingredients applied to transgenic crops compared with conventional crops. In addition, a generic environmental indicator -- the environmental impact quotient (EIQ) -- has been applied by these authors and others to estimate the environmental consequences of the altered pesticide use on transgenic crops. The results show that the predicted environmental impact decreases in transgenic crops. With the advent of new types of agronomic trait and crops that have been genetically modified, it is useful to take also their potential environmental impacts into account.

Health considerations regarding horizontal transfer of microbial transgenes present in genetically modified crops.

The potential effects of horizontal gene transfer on human health are an important item in the safety assessment of genetically modified organisms. Horizontal gene transfer from genetically modified crops to gut microflora most likely occurs with transgenes of microbial origin. The characteristics of microbial transgenes other than antibiotic-resistance genes in market-approved genetically modified crops are reviewed. These characteristics include the microbial source, natural function, function in genetically modified crops, natural prevalence, geographical distribution, similarity to other microbial genes, known horizontal transfer activity, selective conditions and environments for horizontally transferred genes, and potential contribution to pathogenicity and virulence in humans and animals. The assessment of this set of data for each of the microbial genes reviewed does not give rise to health concerns. We recommend including the above-mentioned items into the premarket safety assessment of genetically modified crops carrying transgenes other than those reviewed in the present study.