Mass spectrometric analysis of digesta does not improve the allergenicity assessment of GM crops.

An investigation of the potential allergenicity of newly expressed proteins in genetically modified (GM) crops comprises part of the assessment of GM crop safety. However, allergenicity is not completely predictable from a definitive assay result or set of protein characteristics, and scientific opinions regarding the data that should be used to assess allergenicity are continuously evolving. Early studies supported a correlation between the stability of a protein exposed to digestive enzymes such as pepsin and the protein's status as a potential allergen, but over time the conclusions of these earlier studies were not confirmed. Nonetheless, many regulatory authorities, including the European Food Safety Authority (EFSA), continue to require digestibility analyses as a component of GM crop risk assessments. Moreover, EFSA has recently investigated the use of mass spectrometry (MS), to make digestion assays more predictive of allergy risk, because it can detect and identify small undigested peptides. However, the utility of MS is questionable in this context, since known allergenic peptides are unlikely to exist in protein candidates intended for commercial development. These protein candidates are pre-screened by the same bioinformatics processes that are normally used to identify MS targets. Therefore, MS is not a standalone allergen identification method and also cannot be used to predict previously unknown allergenic epitopes. Thus, the suggested application of MS for analysis of digesta does not improve the poor predictive power of digestion assays in identifying allergenic risk.

The Effect of Genetically Modified Food on Infertility Indices: A Systematic Review Study.

Background and Objectives. With the increase in the growth of genetically modified (GM) crops, concerns as to the adverse effects of GM crops have risen in the community. The present systematic review seeks to assess the GM plants' potential impacts on the sperm parameters, including sperm head, sperm motility, sperm abnormality, and fertility index. Materials and Methods. A structured literature search was independently performed by three authors on Scopus, Web of Science, PubMed, and Embase in January 2019. A total of 1467 publications were obtained by the search strategy after eliminating the duplicates. Moreover, the review only included articles written in English language. Other pertinent peer-reviewed publications were chosen ("snowballing") from the reference lists in the selected publications. To assess the GM crop effects on infertility, experimental studies designed with the control group were selected. On the basis of abstract screening and full-text reviewing, 39 relevant publications were selected, seven of which were used in our review. To access the quality of articles, we used the Cochrane checklist. The collected articles were scored independently by three authors, and the publications with the eligibility criteria were included in our review. No article was excluded due to quality assessment. Results and Conclusion. Our findings indicated that GM products had no adverse effects on infertility indices such as the sperm head, sperm motility, sperm abnormality, and fertility indices. Long-term research still seems to be strongly necessary to ensure that the use of GM plants does not cause any harm to consumers, especially in infertility area.

Subchronic feeding toxicity studies of drought-tolerant transgenic wheat MGX11-10 in Wistar Han RCC rats.

A subchronic toxicity study were conducted in Wistar Han RCC rats to evaluate the potential health effects of genetically modified (GM), drought-tolerant wheat MGX11-10. Rats were fed a rodent diet formulated with MGX11-10 and were compared with rats fed a diet formulated with its corresponding non-transgenic control Jimai22 and rats fed a basal diet. MGX11-10 and Jimai22 were ground into flour and formulated into diets at concentrations of 16.25, 32.5, or 65%, w/w% and fed to rats (10/sex/group) for 13 weeks. Compared with rats fed Jimai22 and the basal-diet group, no biologically relevant differences were observed in rats fed the GM diet with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, clinical chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, the MGX11-10 diets did not cause any treatment-related effects in rats following at least 90 days of dietary administration as compared with rats fed diets with the corresponding non-transgenic control diet and the basal-diet group. The MGX11-10 diets are considered equivalent to the diets prepared from conventional comparators. The results demonstrated that MGX11-10 wheat is as safe and wholesome as the corresponding non-transgenic control wheat.

Is Opposition to Genetically Modified Food "Morally Absolutist"? A Consequence-Based Perspective.

Genetically modified foods (GMFs) have met with strong opposition for most of their existence. According to one account-the consequence-based perspective (CP)-lay people oppose GMFs because they deem them unsafe as well as of dubious value. The CP is backed by the data and offers a clear solution for easing GMF opposition. However, several scholars have claimed that the CP is faulty, that lay opposition derives from largely nonrational factors and is consequence blind. One recent statement of this, the moral-absolutism perspective (MAP), contends that GMFs' opponents are principled "moral absolutists" who think that GMFs should be banned no matter their value or risk. Herein we critically weigh key arguments for this proposal. We also present five new studies that probed the clearest data that seem to favor the MAP-opponents affirming the statement that GMFs should be "prohibited," no matter their value or risk. These studies jointly show that (a) most presumed absolutists do not understand the key question and/or (b) cannot validly answer it. We show that taking due steps in clarifying the question and screening for those participants who cannot validly answer it cuts down absolutism to near zero. Finally, we demonstrate that helping GMFs' opponents imagine a world wherein GMFs are safe and constructive makes the majority willing to welcome GMFs in this context.

Addressing concerns over the fate of DNA derived from genetically modified food in the human body: A review.

Global commercialization of GM food and feed has stimulated much debate over the fate of GM food-derived DNA in the body of the consumer and as to whether it poses any health risks. We reviewed the fate of DNA derived from GM food in the human body. During mechanical/chemical processing, integrity of DNA is compromised. Food-DNA can survive harsh processing and digestive conditions with fragments up to a few hundred bp detectable in the gastrointestinal tract. Compelling evidence supported the presence of food (also GM food) derived DNA in the blood and tissues of human/animal. There is limited evidence of food-born DNA integrating into the genome of the consumer and of horizontal transfer of GM crop DNA into gut-bacteria. We find no evidence that transgenes in GM crop-derived foods have a greater propensity for uptake and integration than the host DNA of the plant-food. We found no evidence of plant-food DNA function/expression following transfer to either the gut-bacteria or somatic cells. Strong evidence suggested that plant-food-miRNAs can survive digestion, enter the body and affect gene expression patterns. We envisage that this multi-dimensional review will address questions regarding the fate of GM food-derived DNA and gene-regulatory-RNA in the human body.

Assessment of the potential allergenicity of genetically-engineered food crops.

An extensive safety assessment process exists for genetically-engineered (GE) crops. The assessment includes an evaluation of the introduced protein as well as the crop containing the protein with the goal of demonstrating the GE crop is "as-safe-as" non-GE crops in the food supply. One of the evaluations for GE crops is to assess the expressed protein for allergenic potential. Currently, no single factor is recognized as a predictor for protein allergenicity. Therefore, a weight-of-the-evidence approach, which accounts for a variety of factors and approaches for an overall assessment of allergenic potential, is conducted. This assessment includes an evaluation of the history of exposure and safety of the gene(s) source; protein structure (e.g. amino acid sequence identity to human allergens); stability of the protein to pepsin digestion in vitro; heat stability of the protein; glycosylation status; and when appropriate, specific IgE binding studies with sera from relevant clinically allergic subjects. Since GE crops were first commercialized over 20 years ago, there is no proof that the introduced novel protein(s) in any commercialized GE food crop has caused food allergy.

Subchronic toxicity study in rats evaluating genetically modified DAS-81419-2 soybean.

A 90-day feeding study in rats was conducted to evaluate the subchronic oral toxicity of genetically modified (GM) DAS-81419-2 soybean. Wistar rats were fed with diets containing toasted soybean meal produced from DAS-81419-2 soybean grain that expresses the Cry1F, Cry1Ac, and Pat proteins or containing conventional soybean at doses of 30.0%, 15.0%, 7.5%, or 0% (control group) for 90 consecutive days. The general behavior, body weight and food consumption were observed. At the middle and end of the experiment, blood, serum, and urine samples were collected for biochemical assays. At the conclusion of the study, the internal organs were weighed and histopathological examination was completed. The rats exhibited free movement and shiny coats without any abnormal symptoms or abnormal secretions in their noses, eyes, or mouths. There were no adverse effects on body weight in GM soybean groups and conventional soybean groups. No biological differences in hematological, biochemical, or urine indices were observed. No significant differences in relative organ weights were detected between the experimental groups and the control group. No histopathological changes were observed. Under the conditions of this study, DAS-81419-2 soybean did not cause any treatment-related effects in Wistar rats following 90 days of dietary administration.

Skepticism Regarding Vaccine and Gluten-Free Food Safety Among Patients with Celiac Disease and Non-celiac Gluten Sensitivity.

BACKGROUND: There has been a marked increase in the adoption of the gluten-free (GF) diet. AIMS: To query individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) on their beliefs toward the health effects of gluten, and safety of vaccines and GF food products. METHODS: We distributed a Web-based survey to individuals with CD and NCGS on a CD center e-mail list. We used univariate and multivariate analysis to compare responses of respondents with CD and NCGS. RESULTS: The overall response rate was 27% (NCGS n = 217, CD n = 1291). Subjects with NCGS were more likely than those with CD to disagree with the statement that "vaccines are safe for people with celiac disease" (NCGS 41.3% vs. CD 26.4% (p < 0.0001), and were more likely to decline vaccination when offered (30.9 vs. 24.2%, p = 0.007). After adjusting for age and gender, NCGS subjects were more likely than CD subjects to avoid genetically modified (GMO) foods (aOR 2.30; 95% CI 1.71-3.10), eat only organic products (aOR 2.87; 95% CI 2.04-4.03), believe that the FDA is an unreliable source of information (aOR 1.82, 95% CI 1.26-2.64), and believe a GF diet improves energy and concentration (aOR 2.52; 95% CI 1.86-3.43). CONCLUSIONS: Subjects with NCGS were more likely than those with CD to have doubts about vaccine safety and believe in the value of non-GMO and organic foods. Our findings suggest that the lack of reliable information on gluten and its content in food and medications may reinforce beliefs that result in a detriment to public health.

Safety evaluation of DAS-44406-6 soybeans in Wistar rats.

A 90-day in-country feeding trial in Wistar rats was conducted at Tianjin Laboratory in China to assess toxicity of diets containing DAS-44406-6 soybean meal. There were no treatment-related changes observed when compared with the non-GM isoline control groups but histopathologically, 2 of 10 high-dose females were reported to show kidney lesions. However, these findings contrasted with the absence of any treatment-related kidney lesions in 3 separate 90-day toxicity studies previously conducted in Sprague Dawley rats. Strain difference is not expected in the kidney response, and based on the low incidence and contrary evidence from previous studies, it is likely that these lesions were of spontaneous origin, or artefactual. To determine that the lesions observed were not treatment-related in Wistar rats, a specific follow-up confirmatory study was conducted under Good Laboratory Practices (GLP) in the Wistar strain of rats following an identical study design to the Tianjin study. To increase the power of detecting effects, twice the number of animals per group (20/sex/group) were used, and no treatment-related kidney histopathological changes were observed. Based on these results and entire weight of evidence evaluation, it is concluded that the histopathological changes previously noted in the 2 female Wistar rats of Tianjin study were not treatment-related and that DAS-44406-6 soybeans are as safe as conventional non-GM soybeans.

The aryloxyalkanoate dioxygenase-12 (AAD-12) protein is not acutely toxic in mice.

Typically, when a protein is orally toxic, it acts via acute mechanisms, especially at high doses. Therefore, an acute oral toxicity study is considered appropriate for evaluating the safety of transgenic proteins. Soybean plants (events DAS-68416-4 and DAS-444Ø6-6) have been genetically modified to express the aryloxyalkanoate dioxygenase-12 (AAD-12) protein. The AAD-12 protein provides tolerance to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). This paper summarizes the study designs of two acute oral toxicity studies evaluating the AAD-12 protein and reports the results of these studies. No mortalities or adverse effects were observed in mice when AAD-12 was tested up to a limit dose of 5000 mg/kg body weight. Based on the results of these studies, it can be concluded that AAD-12 protein, as expressed in genetically modified DAS-68416-4 and DAS-444Ø6-6 soybeans, lacks acute toxicity via the oral route.

In vitro studies with human intestinal epithelial cell line monolayers for protein hazard characterization.

Evaluating the safety of newly expressed proteins in genetically modified (GM) crops is conducted prior to commercialization to determine whether they could present a hazard upon consumption. A multicomponent, weight of evidence approach has been applied to individual proteins that has often included acute oral toxicology studies. Based on resources required to produce and purify the proteins, the number of animals necessary for these studies and the fact that no evidence of hazard has been observed for any of the proteins tested to date, it is questionable whether acute toxicology studies should be conducted for all proteins. This article reviews the chronology of the acute toxicology study from its origins into application for hazard assessment and classification of individual substances including proteins expressed in GM crops. It further proposes that a physiologic approach using cultured intestinal epithelial cell (IEC) line monolayers as an in vitro model of the gastrointestinal system provides results relevant to the hazard characterization of proteins when necessary. Benefits of this approach would include reduced quantities of proteins for testing and minimization or elimination of animal studies while maintaining confidence in the safety assessment process.

Bioinformatics analysis to assess potential risks of allergenicity and toxicity of HRAP and PFLP proteins in genetically modified bananas resistant to Xanthomonas wilt disease.

Banana Xanthomonas wilt (BXW) disease threatens banana production and food security throughout East Africa. Natural resistance is lacking among common cultivars. Genetically modified (GM) bananas resistant to BXW disease were developed by inserting the hypersensitive response-assisting protein (Hrap) or/and the plant ferredoxin-like protein (Pflp) gene(s) from sweet pepper (Capsicum annuum). Several of these GM banana events showed 100% resistance to BXW disease under field conditions in Uganda. The current study evaluated the potential allergenicity and toxicity of the expressed proteins HRAP and PFLP based on evaluation of published information on the history of safe use of the natural source of the proteins as well as established bioinformatics sequence comparison methods to known allergens (www.AllergenOnline.org and NCBI Protein) and toxins (NCBI Protein). The results did not identify potential risks of allergy and toxicity to either HRAP or PFLP proteins expressed in the GM bananas that might suggest potential health risks to humans. We recognize that additional tests including stability of these proteins in pepsin assay, nutrient analysis and possibly an acute rodent toxicity assay may be required by national regulatory authorities.

Genetically modified foods and allergy.

2015 marked the 25th anniversary of the commercial use and availability of genetically modified crops. The area of planted biotech crops cultivated globally occupies a cumulative two billion hectares, equivalent to twice the land size of China or the United States. Foods derived from genetically modified plants are widely consumed in many countries and genetically modified soybean protein is extensively used in processed foods throughout the industrialised countries. Genetically modified food technology offers a possible solution to meet current and future challenges in food and medicine. Yet there is a strong undercurrent of anxiety that genetically modified foods are unsafe for human consumption, sometimes fuelled by criticisms based on little or no firm evidence. This has resulted in some countries turning away food destined for famine relief because of the perceived health risks of genetically modified foods. The major concerns include their possible allergenicity and toxicity despite the vigorous testing of genetically modified foods prior to marketing approval. It is imperative that scientists engage the public in a constructive evidence-based dialogue to address these concerns. At the same time, improved validated ways to test the safety of new foods should be developed. A post-launch strategy should be established routinely to allay concerns. Mandatory labelling of genetically modified ingredients should be adopted for the sake of transparency. Such ingredient listing and information facilitate tracing and recall if required.

Predicament of Chinese legislation on genetically modified food (GMF) labeling management and solutions - from the perspective of the new food safety law.

BACKGROUND: This paper considers the background of Article 69 of the newly revised Food Safety Law in China in combination with the current situation of Chinese legislation on GMF labeling management, compared with a foreign genetically modified food labeling management system, revealing deficiencies in the Chinese legislation with respect to GMF labeling management, and noting that institutions should properly consider the GMF labeling management system in China. RESULTS: China adheres to the principle of mandatory labeling based on both product and processes in relation to GMFs and implements a system of process-centered mandatory labeling under a negotiation-construction form. However, China has not finally defined the supervision mode of mandatory labeling of GMFs through laws, and this remains a challenge for GMF labeling management when two mandatory labeling modes coexist. CONCLUSION: Since April 2015 and October 1, 2015 when the Food Safety Law was revised and formally implemented respectively, the applicable judicial interpretations and enforcement regulations have not made applicable revisions and only principle-based terms have been included in the Food Safety Law, it is still theoretically and practically difficult for mandatory labeling of GMFs in juridical practices and conflicts between the principle of GMF labeling and the purpose that safeguards consumers' right to know remain. The GMF labeling system should be legislatively and practically improved to an extent that protects consumers' right to know. © 2017 Society of Chemical Industry.

Messages promoting genetic modification of crops in the context of climate change: Evidence for psychological reactance.

Genetic modification (GM) of crops and climate change are arguably two of today's most challenging science communication issues. Increasingly, these two issues are connected in messages proposing GM as a viable option for ensuring global food security threatened by climate change. This study examines the effects of messages promoting the benefits of GM in the context of climate change. Further, it examines whether explicit reference to "climate change," or "global warming" in a GM message results in different effects than each other, or an implicit climate reference. An online sample of U.S. participants (N = 1050) were randomly assigned to one of four conditions: "climate change" cue, "global warming" cue, implicit cue, or control (no message). Generally speaking, framing GM crops as a way to help ensure global food security proved to be an effective messaging strategy in increasing positive attitudes toward GM. In addition, the implicit cue condition led to liberals having more positive attitudes and behavioral intentions toward GM than the "climate change" cue condition, an effect mediated by message evaluations.

A 90-Day Feeding Study in Rats to Assess the Safety of Genetically Engineered Pork.

Our laboratory recently produced genetically engineered (GE) Meishan pigs containing a ZFN-edited myostatin loss-of-function mutant. These GE pigs develop and grow as normal as wild type pigs but produce pork with greater lean yield and lower fat mass. To assess any potential subchronic toxicity risks of this GE pork, a 90-day feeding study was conducted in Sprague-Dawley rats. Rats were randomly divided into five groups, and fed for 90 days with basic diet and basic diets formulated with low dose and high dose pork prepared from wild type pigs and GE pigs, respectively. Animal behaviors and clinical signs were monitored twice daily, and body weight and food consumption were measured and recorded weekly. At days 45 and 90, blood tests (lipid panel, electrolytes, parameters related to liver and kidney functions, and complete blood counts) were performed. Additionally, gross pathology and histopathological analyses were performed for major organs in each group. Data analysis shows that there were no significant differences in growth rate, food consumption, and blood test parameters between rat groups fed with GE pork and wild type pork. Although differences in some liver function parameters (such as aspartate aminotransferase, total proteins, albumin, and alkaline phosphatase) and white blood cell counts (such as lymphocyte percentage and monocyte percentage) were observed between rats fed with high dose GE pork and basic diet, all test results in rats fed with GE pork are in the normal range. Additionally, there are no apparent lesions noted in all organs isolated from rats in all five feeding groups on days 45 and 90. Overall, our results clearly indicate that food consumption of GE pork produced by ZFN-edited myostatin loss-of-function mutant pigs did not have any long-term adverse effects on the health status in rats.