Toxicological evaluation of proteins introduced into food crops

Abstract

This manuscript focuses on the toxicological evaluation of proteins introduced into GM crops to impart desired traits. In many cases, introduced proteins can be shown to have a history of safe use. Where modifications have been made to proteins, experience has shown that it is highly unlikely that modification of amino acid sequences can make a non-toxic protein toxic. Moreover, if the modified protein still retains its biological function, and this function is found in related proteins that have a history of safe use (HOSU) in food, and the exposure level is similar to functionally related proteins, then the modified protein could also be considered to be “as-safe-as” those that have a HOSU. Within nature, there can be considerable evolutionary changes in the amino acid sequence of proteins within the same family, yet these proteins share the same biological function. In general, food crops such as maize, soy, rice, canola etc. are subjected to a variety of processing conditions to generate different food products. Processing conditions such as cooking, modification of pH conditions, and mechanical shearing can often denature proteins in these crops resulting in a loss of functional activity. These same processing conditions can also markedly lower human dietary exposure to (functionally active) proteins. Safety testing of an introduced protein could be indicated if its biological function was not adequately characterized and/or it was shown to be structurally/functionally related to proteins that are known to be toxic to mammals.

Bringing New Plant Varieties to Market: Plant Breeding and Selection Practices Advance Beneficial Characteristics while Minimizing Unintended Changes

“…Prior to making any GM crops, all potential proteins that would be produced by the inserted gene (called a "transgene") are screened using computer algorithms to ensure that they are not similar to known allergens, toxins, antinutritional proteins, disease agents, or pharmacologically active proteins (Delaney et al, 2008;Silvanovich et al, 2009;Hammond et al, 2013). For example, comparing candidate proteins to known allergens is typically done using sequence alignment programs, such as BLAST or FASTA, and by using a so-called sliding eight-amino-acid window search.…”

Scientific Opinion on application EFSA‐GMO‐BE‐2013‐117 for authorisation of genetically modified maize MON 87427 × MON 89034 × NK603 and subcombinations independently of their origin, for food and feed uses, import and processing submitted under Regulation (EC) No 1829/2003 by Monsanto Company

“…The CP4 EPSPS proteins are enzymes acting on the shikimic acid pathway for the biosynthesis of aromatic amino acids in plants, showing high substrate specificity. The two insecticidal proteins (Cry1A.105 and Cry2Ab2) act through cellular receptors found in target insect species, and it is reported that the gastrointestinal tract of mammals, including humans, lacks receptors with high specific affinity to Cry proteins (Hammond et al, 2013;Koch et al, 2015).…”

Safety assessment of dicamba mono-oxygenases that confer dicamba tolerance to various crops

“…A key element of the safety evaluation for introduced proteins in GM crops is a bioinformatic analysis to assess whether the introduced protein shows similarity to known toxins or allergens (Hammond et al, 2013;Kier and Petrick, 2008). Bioinformatics analyses were performed on the translated sequence of the DMO coding sequence in these three DT crops to assess their structural relatedness with known allergens and toxins.…”

“…The guidance for assessing the safety of proteins introduced into a GM crop has been developed and harmonized for more than 20 years (Delaney et al, 2008;Hammond et al, 2013;Herouet et al, 2005;Kier and Petrick, 2008). A weight of evidence approach to protein safety is founded on risk assessment principles that include data from both hazard identification studies and exposure assessments.…”