An overview of the safety and biological effects of <i>Bacillus thuringiensis</i> Cry toxins in mammals

Rubio-Infante, Néstor; Moreno‐Fierros, Leticia

doi:10.1002/jat.3252

Cited by 66 publications

(45 citation statements)

References 120 publications

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“…Rubio-Infante and Moreno-Fierros [52] summarised some findings regarding the Cry1Ac toxin and its effect on the immune system. They classify Cry1Ac as a potent mucosal and systemic immunogen and adjuvant [36, 53].…”

Section: Introductionmentioning

confidence: 99%

“…In a further publication [56], it is shown in more detail how Cry1Ac induces macrophage activation. Rubio-Infante and Moreno-Fierros [52] conclude further risk research is necessary: “(…) the immunogenicity of these proteins and their possible risks in humans after short- and long-term exposure must be determined. Evaluation of the risks of Cry proteins in other systems such as the respiratory and nervous systems is also needed.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, Cry1Ac which is expressed in Intacta soybeans is known to also act as an adjuvant that can boost immune reactions to antigens [52]; thus the Bt toxin can for example enhance the reaction of the immune system to allergens being present in the diet. This is particularly relevant in the case of Bt soybeans, since soybeans (i.e.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Possible health impacts of Bt toxins and residues from spraying with complementary herbicides in genetically engineered soybeans and risk assessment as performed by the European Food Safety Authority EFSA

Then¹,

Bauer-Panskus²

2017

Environ Sci Eur

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BackgroundMON89788 was the first genetically engineered soybean worldwide to express a Bt toxin. Under the brand name Intacta, Monsanto subsequently engineered a stacked trait soybean using MON89788 and MON87701—this stacked soybean expresses an insecticidal toxin and is, in addition, tolerant to glyphosate. After undergoing risk assessment by the European Food Safety Authority (EFSA), the stacked event was authorised for import into the EU in June 2012, including for use in food and feed. This review discusses the health risks associated with Bt toxins present in these genetically engineered plants and the residues left from spraying with the complementary herbicide.ResultsWe have compared the opinion published by EFSA [1] with findings from other publications in the scientific literature. It is evident that there are several issues that EFSA did not consider in detail and which will need further assessment: (1) There are potential combinatorial effects between plant components and other impact factors that might enhance toxicity. (2) It is known that Bt toxins have immunogenic properties; since soybeans naturally contain many allergens, these immunogenic properties raise specific questions. (3) Fully evaluated and reliable protocols for measuring the Bt concentration in the plants are needed, in addition to a comprehensive set of data on gene expression under varying environmental conditions. (4) Specific attention should be paid to the herbicide residues and their interaction with Bt toxins.ConclusionsThe case of the Intacta soybeans highlights several regulatory problems with Bt soybean plants in the EU. Moreover, many of the issues raised also concern other genetically engineered plants that express insecticidal proteins, or are engineered to be resistant to herbicides, or have those two types of traits combined in stacked events. It remains a matter of debate whether the standards currently applied by the risk assessor, EFSA, and the risk manager, the EU Commission, meet the standards for risk analysis defined in EU regulations such as 1829/2003 and Directive 2001/18. While this publication cannot provide a final conclusion, it allows the development of some robust hypotheses that should be investigated further before such plants can be considered to be safe for health and the environment. In general, the concept of comparative risk assessment needs some major revision. Priority should be given to developing more targeted approaches. As shown in the case of Intacta, these approaches should include: (i) systematic investigation of interactions between the plant genome and environmental stressors as well as their impact on gene expression and plant composition; (ii) detailed investigations of the toxicity of Bt toxins; (iii) assessment of combinatorial effects taking into account long-term effects and the residues from spraying with complementary herbicides; (iv) investigation into the impact on the immune and hormonal systems and (v) investigation of the impact on the intestinal microbiome after consumption....

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Possible health impacts of Bt toxins and residues from spraying with complementary herbicides in genetically engineered soybeans and risk assessment as performed by the European Food Safety Authority EFSA

Then¹,

Bauer-Panskus²

2017

Environ Sci Eur

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“…In this regard, compounds that disrupt insects’ energy production (respiration targets) or alter growth and development can be highly effective with the possibility of superior selectivity to insects (Sparks and Nauen 2015). Another interesting option is the genetic modification of crops to express endotoxins such as the Cry protein (δ-endotoxin) produced by the Bacillus thuringiensis , which is toxic to a wide variety of insects (Rubio-Infante and Moreno-Fierros 2016). Commercialization of transgenic crops expressing Cry toxins has increased dramatically since the late 1990’s and this biological insecticide at this point appears to have lower toxicity in vertebrates (Rubio-Infante and Moreno-Fierros 2016).…”

Section: How To Improve Safetymentioning

confidence: 99%

Developmental neurotoxicity of succeeding generations of insecticides

Abreu‐Villaça

Levin

2017

Environment International

132

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Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk.

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“…Rubio-Infante and Moreno-Fierros188 summarized some findings www.efsa.europa.eu/publications 30 EFSA Supporting publication 2019:EN-1551 Rubio-Infante and Moreno-Fierros188 summarized some findings www.efsa.europa.eu/publications 30 EFSA Supporting publication 2019:EN-1551…”

mentioning

confidence: 99%

Literature review in support of adjuvanticity/immunogenicity assessment of proteins

Parenti

Santoro

Río

et al. 2019

EFSA Supporting Publications

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Based on the risk assessment of genetically modified plants, according to Implementing Regulation (EU) No 503/201321 "In cases when known functional aspects of the newly expressed protein or structural similarity to known strong adjuvants may indicate possible adjuvant activity, the applicant shall assess the possible role of these proteins as adjuvants". To further investigate the topic, an EFSA procurement was launched requesting a comprehensive literature review and critically appraisal on adjuvanticity and immunogenicity of proteins. A systematic literature search and critical review was performed, identifying 299 relevant publications. From the evaluation of the relevant literature emerged that: i) a clear classification of adjuvant and immunogens of proteins cannot be done; ii) structural features able to modulate adjuvanticity and immunogenicity are mainly ascribed to therapeutic proteins and in the context of allergenicity and cross-reactivity; iii) factors affecting the propensity of a protein to stimulate immune response are aggregation, thermal processing, digestion, food matrix, among others; iv) different proteins are described to have immunomodulatory effects; v) risk assessment of adjuvant and immunogenic behaviour of proteins requires specific methodologies that can be adapted from other fields; vi) adjuvanticity and immunogenicity of Cry proteins in certain experimental conditions seems plausible but due to low dosage, oral route of administration, food and feed processing and digestion, it is unlikely to emerge as a safety issue in food and feed; vii) eliciting an immune response is a very complex matter as the body responds to immune offence by inducing many processes. Based on these considerations, it is expected that the availability of new humanized animal models and the possibility to deploy artificial intelligent systems on the vastity of human data will become a general direction aiming to help answering specific questions relating to the immune systems, including the adjuvanticity and immunogenicity of food/feed proteins.

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An overview of the safety and biological effects of Bacillus thuringiensis Cry toxins in mammals

Cited by 66 publications

References 120 publications

Possible health impacts of Bt toxins and residues from spraying with complementary herbicides in genetically engineered soybeans and risk assessment as performed by the European Food Safety Authority EFSA

Possible health impacts of Bt toxins and residues from spraying with complementary herbicides in genetically engineered soybeans and risk assessment as performed by the European Food Safety Authority EFSA

Developmental neurotoxicity of succeeding generations of insecticides

Literature review in support of adjuvanticity/immunogenicity assessment of proteins

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