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.

The aflatoxin situation in Africa: Systematic literature review.

Contamination of African staple foods is a major issue for human and animal health, nutrition, and trade. This review aimed to collect and synthesize the available evidence on geographical spread, scale of contamination, disease burden, economic impact, and mitigation measures for aflatoxins in Africa by way of a systematic literature review. This knowledge can enhance management strategies for the major challenges to combat aflatoxins. The search was conducted by applying a predefined search strategy, using bibliographic databases and websites, covering the period 2010 to 2018. Results showed that maize, peanuts, and animal feeds were the most studied commodities. For maize, all studies indicated mean AFB1 to exceed the European Union legal limit. From studies on contamination levels and biomarkers, it is clear that overall exposure is high, leading to a substantial increase in long-term disease burden. In addition, concentrations in food occasionally can reach very high levels, causing acute aflatoxicoses. The trade-related impact of aflatoxin contamination was mainly evaluated from the standpoint of aflatoxin regulation affecting products imported from Africa. There was a limited number of studies on health-related economic impacts, pointing out a gap in peer-reviewed literature. A number of mitigation measures have been developed, but proof of cost-effectiveness or even costs alone of the practices is often lacking. We recommend more emphasis to be put in peer-reviewed studies on evidence-based cost-effective mitigation strategies for aflatoxins, on the scale and spread of the problem and its impacts on public health and economics for use in evidence-based policies.

Correction to: Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

In the original publication, the starting point in time for the three feeding trials.

Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.

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.

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.

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.

Does RNAi-Based Technology Fit within EU Sustainability Goals?

European Union (EU) and global sustainability policies emphasize the need to replace contentious pesticides with safe, efficient, and cost-effective alternatives to ensure sustainable food production. However, R&D for alternatives to contentious pesticides are lagging behind and need to be broadened. Here, we discuss how RNAi-based technology can contribute to pesticide risk reduction.

Bioavailability of xenobiotics in the soil environment.

It is often presumed that all chemicals in soil are available to microorganisms, plant roots, and soil fauna via dermal exposure. Subsequent bioaccumulation through the food chain may then result in exposure to higher organisms. Using the presumption of total availability, national governments reduce environmental threshold levels of regulated chemicals by increasing guideline safety margins. However, evidence shows that chemical residues in the soil environment are not always bioavailable. Hence, actual chemical exposure levels of biota are much less than concentrations present in soil would suggest. Because "bioavailability" conveys meaning that combines implications of chemical sol persistency, efficacy, and toxicity, insights on the magnitude of a chemicals soil bioavailability is valuable. however, soil bioavailability of chemicals is a complex topic, and is affected by chemical properties, soil properties, species exposed, climate, and interaction processes. In this review, the state-of-art scientific basis for bioavailability is addressed. Key points covered include: definition, factors affecting bioavailability, equations governing key transport and distributive kinetics, and primary methods for estimating bioavailability. Primary transport mechanisms in living organisms, critical to an understanding of bioavailability, also presage the review. Transport of lipophilic chemicals occurs mainly by passive diffusion for all microorganisms, plants, and soil fauna. Therefore, the distribution of a chemical between organisms and soil (bioavailable proportion) follows partition equilibrium theory. However, a chemical's bioavailability does not always follow partition equilibrium theory because of other interactions with soil, such as soil sorption, hysteretic desorption, effects of surfactants in pore water, formation of "bound residue", etc. Bioassays for estimating chemical bioavailability have been introduced with several targeted endpoints: microbial degradation, uptake by higher plants and soil fauna, and toxicity to organisms. However, there bioassays are often time consuming and laborious. Thus, mild extraction methods have been employed to estimate bioavailability of chemicals. Mild methods include sequential extraction using alcohols, hexane/water, supercritical fluids (carbon dioxide), aqueous hydroxypropyl-beta-cyclodextrin extraction, polymeric TENAX beads extraction, and poly(dimethylsiloxane)-coated solid-phase microextraction. It should be noted that mild extraction methods may predict bioavailability at the moment when measurements are carried out, but not the changes in bioavailability that may occur over time. Simulation models are needed to estimate better bioavailability as a function of exposure time. In the past, models have progressed significantly by addressing each group of organisms separately: microbial degradation, plant uptake via evapotranspiration processes, and uptake of soil fauna in their habitat. This approach has been used primarily because of wide differences in the physiology and behaviors of such disparate organisms. However, improvement of models is badly needed, Particularly to describe uptake processes by plant and animals that impinge on bioavailability. Although models are required to describe all important factors that may affect chemical bioavailability to individual organisms over time (e.g., sorption/desorption to soil/sediment, volatilization, dissolution, aging, "bound residue" formation, biodegradation, etc.), these models should be simplified, when possible, to limit the number of parameters to the practical minimum. Although significant scientific progress has been made in understanding the complexities in specific methodologies dedicated to determining bioavailability, no method has yet emerged to characterized bioavailability across a wide range of chemicals, organisms, and soils/sediments. The primary aim in studying bioavailability is to define options for addressing bioremediation or environmental toxicity (risk assessment), and that is unlikely to change. Because of its importance in estimating research is needed to more comprehensively address the key environmental issue of "bioavailability of chemicals in soil/sediment."

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.

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.

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.

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.

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.

Exposure of livestock to GM feeds: Detectability and measurement.

This review explores the possibilities to determine livestock consumption of genetically modified (GM) feeds/ingredients including detection of genetically modified organism (GMO)-related DNA or proteins in animal samples, and the documentary system that is in place for GM feeds under EU legislation. The presence and level of GMO-related DNA and proteins can generally be readily measured in feeds, using established analytical methods such as polymerase chain reaction and immuno-assays, respectively. Various technical challenges remain, such as the simultaneous detection of multiple GMOs and the identification of unauthorized GMOs for which incomplete data on the inserted DNA may exist. Given that transfer of specific GMO-related DNA or protein from consumed feed to the animal had seldom been observed, this cannot serve as an indicator of the individual animal's prior exposure to GM feeds. To explore whether common practices, information exchange and the specific GM feed traceability system in the EU would allow to record GM feed consumption, the dairy chain in Catalonia, where GM maize is widely grown, was taken as an example. It was thus found that this system would neither enable determination of an animal's consumption of specific GM crops, nor would it allow for quantitation of the exposure.

Surveying selected European feed and livestock production chains for features enabling the case-specific post-market monitoring of livestock for intake and potential health impacts of animal feeds derived from genetically modified crops.

This review, which has been prepared within the frame of the European Union (EU)-funded project MARLON, surveys the organisation and characteristics of specific livestock and feed production chains (conventional, organic, GM-free) within the EU, with an emphasis on controls, regulations, traceability, and common production practices. Furthermore, an overview of the origin of animal feed used in the EU as well as an examination of the use of genetically modified organisms (GMOs) in feed is provided. From the data, it shows that livestock is traceable at the herd or individual level, depending on the species. Husbandry practices can vary widely according to geography and animal species, whilst controls and checks are in place for notifiable diseases and general health symptoms (such as mortality, disease, productive performance). For feeds, it would be possible only to make coarse estimates, at best, for the amount of GM feed ingredients that an animal is exposed to. Labeling requirements are apparently correctly followed. Provided that confounding factors are taken into account, practices such as organic agriculture that explicitly involve the use of non-GM feeds could be used for comparison to those involving the use of GM feed.