转基因抗虫作物对捕食性瓢虫的安全性研究进展

转基因抗虫作物的商业化种植带来了显著的经济、生态和社会效益,对转基因抗虫作物的安全性评价也一直是国内外学者研究的热点。对生物非靶标效应的研究是转基因抗虫作物安全性评价的重要组成部分,农田天敌类生物是其中的重点内容之一。瓢虫是农田生态系统重要的捕食性天敌,评价其在转基因抗虫作物田间是否能通过捕食猎物或取食花粉而接触到杀虫蛋白并富集于体内,进而对自身产生一定的非靶标效应,这对捕食性瓢虫的安全性研究具有重要的意义。本文从捕食性天敌瓢虫的生命表参数、行为功能参数、田间群落参数及体内微环境指标等方面综述了转基因抗虫作物对瓢虫的安全性研究进展,并对后期转基因抗虫作物对田间捕食性天敌的研究方向提出了建议,以期为转基因抗虫作物的环境安全性研究提供理论指导和为进一步完善转基因抗虫作物对瓢虫安全性评价的技术体系提供系统的数据资料。     

Obligatory metabolomic profiling of gene‐edited crops is risk disproportionate

It has been argued that the application of metabolomics to gene‐edited crops would present value in three areas: (i) the detection of gene‐edited crops; (ii) the characterization of unexpected changes that might affect safety; and (iii) building on the track record of rigorous government regulation in supporting consumer acceptance of genetically modified organisms (GMOs). Here, we offer a different perspective, relative to each of these areas: (i) metabolomics is unable to differentiate whether a mutation has resulted from gene editing or from traditional breeding techniques; (ii) it is risk‐disproportionate to apply metabolomics for regulatory purposes to search for possible compositional differences within crops developed using the least likely technique to generate unexpected compositional changes; and (iii) onerous regulations for genetically engineered crops have only contributed to unwarranted public fears, and repeating this approach for gene‐edited crops is unlikely to result in a different outcome. It is also suggested that article proposing the utility of specific analytical techniques to support risk assessment would benefit from the input of scientists with subject matter expertise in risk assessment.     

Calling the tunes on transgenic crops: the case for regulatory harmony

Genetically modified (GM) crops are now grown commercially in 23 countries, with another 29 granting approval for import and release into the environment. Despite the socio-economic and environmental benefits of the technology, further development is being hampered by differences in national regulatory frameworks relating to research, biosafety, and to the trade and use of GM crops. The biosafety regulations in different countries are based on five main international instruments that influence the development of national biosafety systems in terms of field trial permit requirements, risk assessment criteria, labeling, traceability, transparency, public awareness, post-monitoring and import regulations. The global harmonization of data collection, testing procedures and information exchange would help to remove artificial trade barriers, expedite the adoption of GM crops, foster technology transfer and protect developing countries from exploitation, instilling confidence and bringing the benefits of GM products to the consumer.     

转Bt基因抗虫作物对鳞翅目非靶标昆虫生态影响的研究进展

任何转基因作物在进入商业化应用之前都必须经过严格的环境风险评价。评价转基因作物特别是抗虫作物对农田重要非靶标节肢动物的生态影响是其中一项重要内容。当前,全球种植的转基因抗虫作物大多表达对鳞翅目害虫具有活性的Cry1或Cry2类杀虫蛋白。由于非靶标鳞翅目昆虫如斑蝶、家蚕等与靶标害虫具有较近的亲缘关系,其幼虫可能同样对这类杀虫蛋白敏感。因此,这类转基因抗虫作物对非靶标鳞翅目害虫的潜在影响引起了研究者的广泛关注。在总结国内外相关研究数据的基础上,系统分析了转基因抗虫作物对非靶标蝶类和蚕类昆虫的潜在影响,获得以下结论：虽然蚕类和蝶类昆虫对Cry1或Cry2类杀虫蛋白敏感,但在自然条件下这类非靶标昆虫暴露于Cry杀虫蛋白的水平很低,抗鳞翅目害虫转基因作物的种植不可能显著影响田间蝶类昆虫的种群密度,也不会给我国的蚕丝产业带来负面影响。     

Assessment of reproductive risks

In the regulatory process, the hazards posed by potentially toxic agents to the female and male reproductive systems and to developing young are evaluated by risk assessment procedures. In this paper, toxicity testing and the regulatory process are discussed, with emphasis on risk assessment. The suggested testing protocols of the Pesticide Assessment Guidelines (U.S. EPA) are presented as an example of testing that might be done to produce toxicity data for an agent. Protocols and end points that are utilized in testing for reproductive effects are described. Included are acute, subchronic, chronic, and short-term tests. The four components of reproductive risk assessment (hazard identification, dose-response assessment, exposure assessment, and risk characterization) are examined. Effects of dibromochloropropane on rabbit testicular parameters are used to demonstrate approaches that could be taken in doing a reproductive risk assessment. Research needs for screening methods, adequate dose-response testing, toxicokinetics, end point development, and extrapolation methods are identified. Finally, this paper discusses selected areas in which changes in reproductive risk assessment are anticipated, as well as the mechanism for influencing the nature and extent of those changes.     

Making effective use of existing data for case‐by‐case risk assessments of genetically engineered crops

Many crops in developing countries suffer devastating attacks from insect pests. Expression of insecticidal proteins in genetically engineered (GE) crops is a potentially powerful means of controlling such pests. Potentially harmful effects of these crops on non‐target organisms (NTOs) is of major concern as many of those provide important ecological functions such as pest regulation. Consequently, the likelihood of adverse effects of insect‐resistant GE crops on NTOs is assessed case‐by‐case as part of environmental risk assessments that inform regulatory decision‐making. While risk assessments should be rigorous, it is vital that regulatory barriers do not unnecessarily restrict or prevent the application of genetic engineering to important crops in those countries. Efficient regulatory decision‐making should make effective use of published information on the biology and ecology of the crop in the country where approval is sought, along with regulatory data produced for GE insect‐resistant crops that have received regulatory approvals elsewhere. Just as the risks are assessed for each GE crop individually, the amount of new regulatory data required for a GE crop should vary between crops depending on the amount of existing data and the severity of the perceived risks: new data should be collected only if existing data do not corroborate identified risk hypotheses with sufficient certainty. In this paper, we illustrate how such an approach could work using risks to NTOs from insect‐resistant GE pigeonpea in India as an example.     

Brazil and the development of international scientific biosafety testing guidelines for transgenic crops

Under the umbrella of the International Organisation of Biological Control (IOBC), an international working group of public sector scientists entitled on "Transgenic Organisms in Integrated Pest Management and Biological Control" has been organized. The group will develop scientific principles and detailed scientific guidelines for biosafety testing of transgenic crops. The key elements of this project are: (1) An international initiative including expert scientists from leading research institutions in developed and developing countries; (2) coordination of the development and implementation of the guidelines as a dynamic process, which will include scientific and technical capacity building and communication among scientists and between scientists and policy makers; (3) rapid serial publication of sections of the guidelines as they are completed; and (4) rapid and timely revision of previously published sections. The guidelines will be constructed on a case-by-case basis and will have no regulatory legitimacy themselves.     

The release of genetically modified crops into the environment. Part I. Overview of current status and regulations

In the past 6 years, the global area of commercially grown, genetically modified (GM) crops has increased more than 30-fold to over 52 million hectares. The number of countries involved has more than doubled. Especially in developing countries, the GM crop area is anticipated to increase rapidly in the coming years. Despite this high adoption rate and future promises, there is a multitude of concerns about the impact of GM crops on the environment. Regulatory approaches in Europe and North America are essentially different. In the EU, it is based on the process of making GM crops; in the US, on the characteristics of the GM product. Many other countries are in the process of establishing regulation based on either system or a mixture. Despite these differences, the information required for risk assessment tends to be similar. Each risk assessment considers the possibility, probability and consequence of harm on a case-by-case basis. For GM crops, the impact of non-use should be added to this evaluation. It is important that the regulation of risk should not turn into the risk of regulation. The best and most appropriate baseline for comparison when performing risk assessment on GM crops is the impact of plants developed by traditional breeding. The latter is an integral and accepted part of agriculture.     

Advancing environmental risk assessment for transgenic biofeedstock crops

Transgenic modification of plants is a key enabling technology for developing sustainable biofeedstocks for biofuels production. Regulatory decisions and the wider acceptance and development of transgenic biofeedstock crops are considered from the context of science-based risk assessment. The risk assessment paradigm for transgenic biofeedstock crops is fundamentally no different from that of current generation transgenic crops, except that the focus of the assessment must consider the unique attributes of a given biofeedstock crop and its environmental release. For currently envisioned biofeedstock crops, particular emphasis in risk assessment will be given to characterization of altered metabolic profiles and their implications relative to non-target environmental effects and food safety; weediness and invasiveness when plants are modified for abiotic stress tolerance or are domesticated; and aggregate risk when plants are platforms for multi-product production. Robust risk assessments for transgenic biofeedstock crops are case-specific, initiated through problem formulation, and use tiered approaches for risk characterization.     

Photochemical genotoxicity: principles and test methods. Report of a GUM task force

In recent years, assessing the photogenotoxic potential of a compound became an issue for certain drugs and cosmetical products. Therefore, existing methods performed according to international guidelines (e.g. OECD guidelines) were adapted to the use of concurrent UV-visible (UV-Vis) light irradiation for the assessment of photomutagenicity/photogenotoxicity. In this review, photobiological bases of the processes occurring in the cell after irradiation with UV- and/or visible (vis)-light as well as a compilation of testing methods is presented. Methods comprise cell free investigations on naked DNA and in vitro methods, such as the photo-Ames test, the photo-HPRT/photo-mouse lymphoma assay (MLA), the photo-micronucleus test (MNT), the photo-chromosomal aberration test (CA) and the photo-Comet assay. A compilation of the currently available international literature of compounds tested on photogenotoxicity is given for each method. The state of the art of photogenotoxicity testing as well as the rational for testing are outlined in relation to the recommendations reached in expert working groups at different international meetings and to regulatory guidance papers. Finally, photogenotoxicity testing as predictor of photocarcinogenicity and in the light of risk assessment is discussed.     

Genotoxicity risk assessment: a proposed classification strategy

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines for Mutagenicity Risk Assessment in 1986 that focused mainly on transmissible germ cell genetic risk. Somatic cell genetic risk has also been a risk consideration, usually in support of carcinogenicity assessments. EPA and other international regulatory bodies have published mutagenicity testing requirements for agents (pesticides, pharmaceuticals, etc.) to generate data for use in genotoxicity risk assessments. The scheme that follows provides a proposed harmonization approach in which genotoxicity assessments are fully developed within the risk assessment paradigm used by EPA, and sets out a process that integrates newer thinking in testing battery design with the risk assessment process. A classification strategy for agents based on inherent genotoxicity, dose-responses observed in the data, and an exposure analysis is proposed. The classification leads to an initial level of concern for genotoxic risk to humans. A total risk characterization is performed using all relevant toxicity data and a comprehensive exposure evaluation in association with the genotoxicity data. The result of this characterization is ultimately used to generate a final level of concern for genotoxic risk to humans. The final level of concern and characterized genotoxicity risk assessment are communicated to decision makers for possible regulatory action(s) and to the public.     

Genotoxicity risk assessment: a proposed classification strategy

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines for Mutagenicity Risk Assessment in 1986 that focused mainly on transmissible germ cell genetic risk. Somatic cell genetic risk has also been a risk consideration, usually in support of carcinogenicity assessments. EPA and other international regulatory bodies have published mutagenicity testing requirements for agents (pesticides, pharmaceuticals, etc.) to generate data for use in genotoxicity risk assessments. The scheme that follows provides a proposed harmonization approach in which genotoxicity assessments are fully developed within the risk assessment paradigm used by EPA, and sets out a process that integrates newer thinking in testing battery design with the risk assessment process. A classification strategy for agents based on inherent genotoxicity, dose-responses observed in the data, and an exposure analysis is proposed. The classification leads to an initial level of concern for genotoxic risk to humans. A total risk characterization is performed using all relevant toxicity data and a comprehensive exposure evaluation in association with the genotoxicity data. The result of this characterization is ultimately used to generate a final level of concern for genotoxic risk to humans. The final level of concern and characterized genotoxicity risk assessment are communicated to decision makers for possible regulatory action(s) and to the public.     

Replicating viral vectors as HIV vaccines: Summary report from the IAVI-sponsored satellite symposium at the AIDS vaccine 2009 conference

In October 2009, The International AIDS Vaccine Initiative (IAVI) convened a satellite symposium entitled ‘Replicating Viral Vectors for use in AIDS Vaccines’ at the AIDS Vaccine 2009 Conference in Paris. The purpose of the symposium was to gather together researchers, representatives from regulatory agencies, and vaccine developers to discuss issues related to advancement of replication-competent viral vector- based HIV vaccines into clinical trials. The meeting introduced the rationale for accelerating the development of replicating viral vectors for use as AIDS vaccines. It noted that the EMEA recently published draft guidelines that are an important first step in providing guidance for advancing live viral vectors into clinical development. Presentations included case studies and development challenges for viral vector-based vaccine candidates. These product development challenges included cell substrates used for vaccine manufacturing, the testing needed to assess vaccine safety, conducting clinical trials with live vectors, and assessment of vaccination risk versus benefit. More in depth discussion of risk and benefit highlighted the fact that AIDS vaccine efficacy trials must be conducted in the developing world where HIV incidence is greatest and how inequities in global health dramatically influence the political and social environment in developing countries.     

Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals

The local lymph node assay (LLNA) is a murine model developed to evaluate the skin sensitization potential of chemicals. The LLNA is an alternative approach to traditional guinea pig methods and in comparison provides important animal welfare benefits. The assay relies on measurement of events induced during the induction phase of skin sensitization, specifically lymphocyte proliferation in the draining lymph nodes which is a hallmark of a skin sensitization response. Since its introduction the LLNA has been the subject of extensive evaluation on a national and international scale, and has been successfully validated and incorporated worldwide into regulatory guidelines. Experience gained in recent years has demonstrated that adherence to published procedures and guidelines for the LLNA (e.g., with respect to dose and vehicle selection) is critical for the successful conduct and eventual interpretation of the data. In addition to providing a robust method for skin sensitization hazard identification, the LLNA has proven very useful in assessing the skin sensitizing potency of test chemicals, and this has provided invaluable information to risk assessors. The primary method to make comparisons of the relative potency of chemical sensitizers is to use linear interpolation to estimate the concentration of chemical required to induce a stimulation index of three relative to concurrent vehicle-treated controls (EC3). In certain situations where there are available less than optimal dose response data a log-linear extrapolation method can be used to estimate an EC3 value which can reduce significantly the need for repeat testing of chemicals. The LLNA, when conducted according to published guidelines, provides a robust method for skin sensitization testing that not only provides reliable hazard identification information but also data necessary for effective risk assessment and risk management.     

An Assessment of Integrated Risk Assessment

In order to promote international understanding and acceptance of the integrated risk assessment process, the World Health Organization/International Programme on Chemical Safety (WHO/IPCS), in collaboration with the U.S. Environmental Protection Agency and the Organization for Economic Cooperation and Development, initiated a number of activities related to integrated risk assessment. In this project, the WHO/IPCS defines integrated risk assessment as a science-based approach that combines the processes of risk estimation for humans, biota, and natural resources in one assessment. This article explores the strengths and weaknesses of integration as identified up to this date and the degree of acceptance of this concept by the global risk assessment/risk management community. It discusses both opportunities and impediments for further development and implementation.

The major emerging opportunities for an integrated approach stem from the increasing societal and political pressure to move away from vertebrate testing leading to a demand for scientific integrated approaches to in vitro and in vivo testing, as well as to computer simulations, in so-called Intelligent Testing Strategies. In addition, by weighing the evidence from conventional mammalian toxicology, ecotoxicology, human epidemiology, and eco-epidemiology, risk assessors could better characterize mechanisms of action and the forms of the relationships of exposures to responses. It is concluded that further demonstrations of scientific, economic and regulatory benefits of an integrated approach are needed. As risk assessment is becoming more mechanistic and molecular this may create an integrated approach based on common mechanisms and a common systems-biology approach.     

Biosafety management and commercial use of genetically modified crops in China

As a developing country with relatively limited arable land, China is making great efforts for development and use of genetically modified (GM) crops to boost agricultural productivity. Many GM crop varieties have been developed in China in recent years; in particular, China is playing a leading role in development of insect-resistant GM rice lines. To ensure the safe use of GM crops, biosafety risk assessments are required as an important part of the regulatory oversight of such products. With over 20 years of nationwide promotion of agricultural biotechnology, a relatively well-developed regulatory system for risk assessment and management of GM plants has been developed that establishes a firm basis for safe use of GM crops. So far, a total of seven GM crops involving ten events have been approved for commercial planting, and 5 GM crops with a total of 37 events have been approved for import as processing material in China. However, currently only insect-resistant Bt cotton and disease-resistant papaya have been commercially planted on a large scale. The planting of Bt cotton and disease-resistant papaya have provided efficient protection against cotton bollworms and Papaya ringspot virus (PRSV), respectively. As a consequence, chemical application to these crops has been significantly reduced, enhancing farm income while reducing human and non-target organism exposure to toxic chemicals. This article provides useful information for the colleagues, in particular for them whose mother tongue is not Chinese, to clearly understand the biosafety regulation and commercial use of genetically modified crops in China.     

Risk predisposition for Crohn disease: a "ménage à trois" combining IRGM allele, miRNA and xenophagy

Susceptibility to Crohn disease (CD), an inflammatory bowel disease, is influenced by common variants at many loci like the exonic synonymous IRGM SNP (rs10065172, NM_001145805.1, c.313C>T). We recently showed that miR-196 is overexpressed in the inflammatory intestinal epithelia of individuals with CD and downregulates the IRGM protective (c.313C) but not the risk-associated (c.313T) allele. Eventually, loss of: IRGM/miRNA regulation compromises xenophagy. These results highlight a critical "ménage à trois" in risk susceptibility combining IRGM allele, miRNA and xenophagy.     

Removing politics from innovations that improve food security

Genetically modified (GM) organisms and crops have been a feature of food production for over 30 years. Despite extensive science-based risk assessment, the public and many politicians remain concerned with the genetic manipulation of crops, particularly food crops. Many governments have addressed public concern through biosafety legislation and regulatory frameworks that identify and regulate risks to ensure human health and environmental safety. These domestic regulatory frameworks align to international scientific risk assessment methodologies on a case-by-case basis. Regulatory agencies in 70 countries around the world have conducted in excess of 4400 risk assessments, all reaching the same conclusion: GM crops and foods that have been assessed provide no greater risk to human health or the environment than non-GM crops and foods. Yet, while the science regarding the safety of GM crops and food appears conclusive and societal benefits have been globally demonstrated, the use of innovative products have only contributed minimal improvements to global food security. Regrettably, politically-motivated regulatory barriers are currently being implemented with the next genomic innovation, genome editing, the implications of which are also discussed in this article. A decade of reduced global food insecurity was witnessed from 2005 to 2015, but regrettably, the figure has subsequently risen. Why is this the case? Reasons have been attributed to climate variability, biotic and abiotic stresses, lack of access to innovative technologies and political interference in decision making processes. This commentary highlights how political interference in the regulatory approval process of GM crops is adversely affecting the adoption of innovative, yield enhancing crop varieties, thereby limiting food security opportunities in food insecure economies.

     

History of safe exposure and bioinformatic assessment of phosphomannose-isomerase (PMI) for allergenic risk

Newly expressed proteins in genetically engineered crops are evaluated for potential cross reactivity to known allergens as part of their safety assessment. This assessment uses a weight-of-evidence approach. Two key components of this allergenicity assessment include any history of safe human exposure to the protein and/or the source organism from which it was originally derived, and bioinformatic analysis identifying amino acid sequence relatedness to known allergens. Phosphomannose-isomerase (PMI) has been expressed in commercialized genetically engineered (GE) crops as a selectable marker since 2010 with no known reports of allergy, which supports a history of safe exposure, and GE events expressing the PMI protein have been approved globally based on expert safety analysis. Bioinformatic analyses identified an eight-amino-acid contiguous match between PMI and a frog parvalbumin allergen (CAC83047.1). While short amino acid matches have been shown to be a poor predictor of allergen cross reactivity, most regulatory bodies require such matches be assessed in support of the allergenicity risk assessment. Here, this match is shown to be of negligible risk of conferring cross reactivity with known allergens.

     

Risk predisposition for Crohn disease: A “ménage à trois” combining IRGM allele,miRNA and xenophagy

Susceptibility to Crohn disease (CD), an inflammatory bowel disease, is influenced by common variants at many loci like the exonic synonymous IRGM SNP (rs10065172, NM_001145805.1, c.313C>T). We recently showed that miR-196 is overexpressed in the inflammatory intestinal epithelia of individuals with CD and downregulates the IRGM protective (c.313C) but not the risk-associated (c.313T) allele. Eventually, loss of

IRGM/miRNA regulation compromises xenophagy. These results highlight a critical “ménage à trois” in risk susceptibility combining IRGM allele, miRNA and xenophagy.