The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations

May combine two claims.

There is international disagreement across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements.

“There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements.”

May combine two claims.

In many jurisdictions regulatory guidelines do not specify a requirement for WF toxicity studies but are generally sufficiently flexible to allow for such a study to be requested on a case-by-case basis.

“In many jurisdictions regulatory guidelines do not specify a requirement for WF toxicity studies but are generally sufficiently flexible to allow for such a study to be requested on a case-by-case basis.”

May combine two claims.

Whole food toxicity studies, or a justification for their omission, are explicitly required as a routine component of the data package for regulatory approval of GM food in some jurisdictions (e.g. Europe), but are not required in others (e.g. Australia), while still others do not regulate GM food separately to food developed by other processes (e.g. USA).

“Whole food toxicity studies, or a justification for their omission, are explicitly required as a routine component of the data package for regulatory approval of GM food in some jurisdictions (e.g. Europe), but are not required in others (e.g. Australia), while still others do not regulate GM food separately to food developed by other processes (e.g. USA).”

May combine two claims.

There is no international consensus on the need for animal studies in support of the safety of GM food or feed, on the circumstances that might trigger a requirement for a WF toxicity study, on the design of such studies, or on how the results might be reliably interpreted.

“it is clear from Table 1 that there is no international consensus on the need for animal studies in support of the safety of GM food or feed or on the circumstances that might trigger a requirement for a WF toxicity study, on the design of such studies, or on how the results might be reliably interpreted.”

Classified as probably not a substantial claim.

Among jurisdictions that require formal safety assessment of GM food and feed, differences exist between those that have concluded that WF toxicity studies are not scientifically justified, such as Australia, and those that have concluded they provide useful information for safety assessment, such as Europe.

“Similarly, among jurisdictions that do require formal safety assessment of GM food and feed, differences exist between those that have concluded that WF toxicity studies are not scientifically justified, such as Australia, and those that have concluded they provide useful information for safety assessment, such as Europe.”

May combine two claims.

A substantial number of animal studies have been conducted on commercial GM crops as a component of their safety assessment and as a component of research on the design and utility of WF studies for food risk assessment.

“A substantial number of animal studies have been conducted on commercial GM crops as a component of their safety assessment, and as a component of research on the design and utility of WF studies for food risk assessment.”

May combine two claims.

In many of the cited transgenic plant examples, the phenotype was consistent with the targeted pathway or due to better plant health.

“Second, in many cases, the phenotype was consistent with the targeted pathway or due to better plant health.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

No adverse findings have been identified in livestock and poultry feeding studies of GM crops.

“These types of studies are not considered further in this review, although notably, no adverse findings have been identified in studies of this type.”

May combine two claims.

The WF toxicity studies reviewed here have characteristics that contribute to unreliable results: small study size, small effect sizes relative to background variability, and large numbers of parameters tested unrelated to a specific prior hypothesis.

“Key contributors to unreliable results include; small study size, small effect sizes in relation to background variability, and large numbers of parameters being tested that are unrelated to a specific prior hypothesis. All are characteristics of the WF toxicity studies reviewed here.”

May combine two claims.

Dietary incorporation of test crops at levels greater than 60% (w/w) have been achieved, although levels in the range of 30% (w/w) are more common.

“Dietary incorporation of test crops at levels greater than 60% (w/w) have been achieved, although levels in the range of 30% (w/w) are more common (Table 4).”

May combine two claims.

The inherently low toxicological power of WF toxicity studies and/or flawed study design and failure to consider the limitations of WF toxicity studies have resulted in a number of studies of GM crops in which the data have been misinterpreted, or misrepresented, as showing adverse effects.

“The inherently low toxicological power of WF toxicity studies and/or flawed study design and failure to consider the limitations of WF toxicity studies have resulted in a number of studies of GM crops in which the data have been misinterpreted, or misrepresented, as showing adverse effects (Table 5).”

May combine two claims.

The control mice in the Malatesta et al. studies received 14% 'wild type' soybean in their diet, with no indication of the variety or origin of either the GM or non-GM soy used.

“The control mice received 14% “wild type” soybean in their diet, with no indication of the variety or origin of either the GM or non-GM soy used.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The Joint FAO/IAEA/WHO Study Group concluded that subchronic, chronic, and carcinogenicity studies demonstrated no short- or long-term toxicity due to irradiated food consumption.

“The Joint FAO/IAEA/WHO Study Group (WHO, 1999) did not directly address the strengths or limitations of whole food studies, but considered that animal studies were suitable models and concluded that subchronic, chronic, and carcinogenicity studies demonstrated no short- or long-term toxicity due to irradiated food consumption.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Unintended changes may be either explicable or inexplicable based on current knowledge of plant biology, genetics, and/or metabolism and are therefore not necessarily unexpected.

“Unintended changes may be either explicable or inexplicable based on our current knowledge of plant biology, genetics, and/or metabolism (Cellini et al., 2004) and are therefore not necessarily unexpected.”

• cites Cellini et al., 2004 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

WF animal toxicity studies are unnecessary and scientifically unjustifiable.

“the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.”

May combine two claims.

The concordance between predictions of safety based on crop genetics and compositional analyses and results of well-conducted animal testing is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general.

“However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general.”

Classified as probably not a substantial claim.

The comparison of a GM crop to its most closely related conventional counterpart, based on agronomic performance metrics and comprehensive, crop-specific compositional analysis of known nutrients, anti-nutrients, and toxicants for that crop species, is the primary basis of the safety assessment.

“The comparison of a GM crop to its most closely related conventional counterpart, based on agronomic performance metrics and comprehensive, crop-specific compositional analysis of known nutrients, anti-nutrients, and toxicants for that crop species, is the primary basis of the safety assessment.”

• cites Codex Alimentarius Commission, 2009Not checked yet

  Not checked in the free run.

• cites ILSI, 2004Not checked yet

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• AssumptionThe authors state this as an assumption: The conventional comparator is safe to consume based on a history of safe use.

Probably not a substantial claim: may not pass S3 (load-bearing).

The FAO/IAEA/WHO expert group recognized the value of chemical studies as a basis for evaluating the wholesomeness of irradiated foods.

“and that “the committee … also recognized the value of chemical studies as a basis for evaluating the wholesomeness of irradiated foods” (WHO, 1999).”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

A large body of research and experience enables a comparison of the relative strengths and limitations of WF toxicity studies and crop compositional analyses to predict risks to human health.

“More generally, a large body of research and experience enables a comparison of the relative strengths and limitations of WF toxicity studies and crop compositional analyses to predict risks to human health.”

Classified as probably not a substantial claim.

Foods and feeds derived from GM crops must be shown, prior to commercialization, to be as safe as those derived from conventional crops that have an established history of safe use.

“Foods and feeds derived from GM crops must be shown, prior to commercialization, to be as safe as those derived from conventional crops that have an established history of safe use.”

• cites Codex Alimentarius Commission, 2009Not checked yet

  Not checked in the free run.

• cites ILSI, 2004Not checked yet

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Probably not a substantial claim: may not pass S4 (based). May combine two claims.

A considerable number of WF toxicity studies have now been conducted on GM food and feed, which provide sufficient data to consider the nature, extent, and value of the results of those studies and whether they have materially added to the safety assessment of GM crops.

“A considerable number of WF toxicity studies have now been conducted on GM food and feed, which provide sufficient data to consider the nature, extent, and value of the results of those studies and whether they have materially added to the safety assessment of GM crops.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The FAO/IAEA/WHO expert group concluded that the determination of wholesomeness for a representative food could be extrapolated to other foods of similar composition on the basis of available chemical data, without animal testing.

“The FAO/IAEA/WHO expert group also concluded, however, that “the determination of wholesomeness for a representative food could be extrapolated to other foods of similar composition on the basis of available chemical data” (i.e. without animal testing)”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In some cases, the safety of intended changes in specific nutrients or anti-nutrients in a GM crop has been assessed in an animal model.

“In some cases, the safety of intended changes in specific nutrients or anti-nutrients in a GM crop has been assessed in an animal model (Hammond et al., 2008).”

• cites Hammond et al., 2008Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

The lack of consensus among food regulators on WF toxicity studies reflects differences in regulatory philosophy, founded in sociopolitical as well as scientific considerations, and differences in perceptions of both the need for safety assessment of GM foods and feeds in general and the scientific value of WF toxicity studies specifically.

“This lack of consensus reflects differences in regulatory philosophy, founded in sociopolitical as well as scientific considerations, and differences in perceptions of both the need for safety assessment of GM foods and feeds in general and the scientific value of WF toxicity studies specifically.”

Probably not a substantial claim: may not pass S4 (based).

A wealth of highly relevant data has been generated from animal studies of WFs treated by irradiation.

“A wealth of highly relevant data has also been generated from animal studies of WFs treated by irradiation.”

May combine two claims.

Over a number of decades, animal studies were conducted on whole irradiated foods, involving the sacrifice of tens of thousands of laboratory animals, mostly rats and mice, but also dogs, hamsters, quail, primates, and chickens.

“Over a number of decades, animal studies were conducted on whole irradiated foods, involving the sacrifice of tens of thousands of laboratory animals, mostly rats and mice, but also dogs, hamsters, quail, primates, and chickens.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The search algorithm contained keywords "whole food", "toxicity study", "subchronic" and "90-day", in combination with "genetically modified", "GM", "rodents", "rats", "safety".

“The search algorithm contained the following keywords; “whole food”, “toxicity study”, “subchronic” and “90-day”, in combination with the keywords: “genetically modified”, “GM”, “rodents”, “rats”, “safety”.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The nature of the radiolytic products from food irradiation did not differ substantially from those generated by conventional cooking of foods.

“They also noted that the nature of the radiolytic products from food irradiation did not differ substantially than those generated by conventional cooking of foods.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Those genetic changes caused by the transformation process that might produce deleterious off-types or other undesirable phenotypic changes will generally be eliminated.

“Those genetic changes caused by the transformation process that might produce deleterious off-types or other undesirable phenotypic changes will generally be eliminated.”

Classified as probably not a substantial claim.

The review's references were identified by searching PubMed, SCOPUS, Google Scholar, AGRICOLA, PASCAL, CABA, FROSTI, LIFESCI, PQSCITECH, BIOSIS, FSTA, CA, ESBIOBASE, BIOENG, COMPENDEX, EMBASE and SCISEARCH for articles published between January 2004 and June 2013.

“For the purpose of the present review, references incorporated in the tables were identified using the following databases: PubMed, SCOPUS, Google Scholar, AGRICOLA, PASCAL, CABA, FROSTI, LIFESCI, PQSCITECH, BIOSIS, FSTA, CA, ESBIOBASE, BIOENG, COMPENDEX, EMBASE and SCISEARCH for articles published between January 2004 and June 2013.”

Probably not a substantial claim: may not pass S3 (load-bearing).

References consisting only of an abstract were not considered.

“References consisting only of an abstract were not considered.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Because livestock and poultry feeding studies are conducted in the species that the GM crop is destined to feed, issues of extrapolation for human health risk assessment are not applicable.

“Because they are conducted in the species that the GM crop is destined to feed, issues of extrapolation for human health risk assessment are not applicable.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The concept of substantial equivalence as applied to GM crop safety assessment was first described by the OECD (1993), and the approach has been supported by international scientific authorities such as the FAO/WHO (2000), Codex Alimentarius Commission (2009), and EFSA (2008a).

“The concept of substantial equivalence as applied to GM crop safety assessment was first described by the OECD (1993), and the approach has been supported by international scientific authorities such as the FAO/WHO (2000), Codex Alimentarius Commission (2009), and EFSA (2008a).”

• cites OECD (1993)Not checked yet

  Not checked in the free run.

• cites FAO/WHO (2000)Not checked yet

  Not checked in the free run.

• cites Codex Alimentarius Commission (2009)Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Where a study was available both as an opinion or evaluation by a regulatory agency and as a paper in the peer reviewed literature, the latter was cited but both were considered.

“Similarly where a study was available both as an opinion or evaluation by a regulatory agency and as a paper in the peer reviewed literature, the latter has been cited but both have been considered.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Although vast numbers of WF animal studies were conducted on a wide range of irradiated foods using various levels of irradiation, none of the toxicological studies produced evidence of adverse effects.

“Thus, although vast numbers of WF animal studies were conducted on a wide range of irradiated foods using various levels of irradiation, “none of the toxicological studies … had produced evidence of adverse effects …””

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The process of developing a GM plant variety is closely analogous to conventional crop breeding.

“The process of developing a GM plant variety is closely analogous to conventional crop breeding.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The goal of comparative assessment is to investigate intended and unintended changes in the GM crop relative to conventional, non-GM comparator crops with respect to agronomic, molecular, and compositional characteristics.

“The goal of comparative assessment is to investigate intended and unintended changes in the GM crop relative to conventional, non-GM comparator crops with respect to agronomic, molecular, and compositional characteristics.”

Probably not a substantial claim: may not pass S3 (load-bearing).

For regulators, comparative safety assessment is the driving principal of GM crop safety assessment.

“For regulators, comparative safety assessment is the driving principal of GM crop safety assessment.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The expert committee concluded that the application of "risk assessment" in the currently accepted sense is not appropriate to the toxicological assessment of foods preserved by high-dose irradiation, and that the concept of "substantial equivalence" may be more appropriate.

“the expert committee (WHO, 1999) concluded the following:The application of “risk assessment” in the currently accepted sense is not appropriate to the toxicological assessment of foods preserved by high-dose irradiation. In this context, the concept of “substantial equivalence” may be more appropriate.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Only feeding studies, not studies using gavage or other routes of administration, were considered.

“Only feeding studies and not studies using gavage or other routes of administration were considered.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The compositional, morphological, and agronomic characteristics of a crop plant are the culmination of the coordinated expression of multiple genes that produce enzymes, structural components, regulatory proteins and nucleic acids, and metabolites.

“The compositional, morphological, and agronomic characteristics of a crop plant are the culmination of the coordinated expression of multiple genes that produce enzymes, structural components, regulatory proteins and nucleic acids, and metabolites.”

May combine two claims.

Genetic manipulation by conventional breeding may also introduce unintended changes to crops, as does the natural variation in climatic and agricultural conditions for a crop grown across dispersed regions of the world.

“Notably, genetic manipulation by conventional breeding may also introduce unintended changes to crops (Cellini et al., 2004; Kuiper & Kleter, 2003) as does the natural variation in climatic and agricultural conditions for a crop grown across dispersed regions of the world.”

• cites Cellini et al., 2004 sourceNot checked yet

  Not checked in the free run.

• cites Kuiper & Kleter, 2003Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The search was completed by a review of each paper to complete Tables 2-4, to identify study parameters of interest including number of animals, endpoints, duration, and others.

“This search was completed by a review of each paper to complete Tables 2–4, to identify study parameters of interest in the context of this review, including number of animals, endpoints, duration, and others.”

Probably not a substantial claim: may not pass S3 (load-bearing).

WF toxicity studies are triggered by concern that an intended change may be accompanied by unintended change(s) not identifiable by compositional, agronomic, or molecular comparison of the GM crop with appropriate conventional comparators.

“These studies are triggered by concern that an intended change may be accompanied by unintended change(s) not identifiable by compositional, agronomic, or molecular comparison of the GM crop with appropriate conventional comparators.”

Classified as probably not a substantial claim.

The statistical power of a toxicology study is determined by the numbers of animals per group, the underlying background variation, and the size of the effect produced by the test material.

“The statistical power of a toxicology study is determined by the interplay of three key parameters: the numbers of animals in each group to be compared, the underlying background variation in the value of a given parameter in the species population being studied, and the size of the effect produced by the test material administered.”

Probably not a substantial claim: may not pass S2 (checkable).

Recognition of common pathologies is essential in avoiding misinterpretation of changes in treated animals that may be inherent in the animal model and not due to treatment.

“Recognition of common pathologies is essential in avoiding misinterpretation of changes in treated animals that may be inherent in the animal model and not due to treatment.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent review of long-term WF toxicity studies concluded that GM food is not revealed to be harmful when the duration of feeding is increased to well over 90 days.

“However, a conclusion of a recent review of long term WF toxicity studies is that GM food is not revealed to be harmful when the duration of feeding is increased to well over 90 days (Snell et al., 2012).”

• cites Snell et al., 2012 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The considerable available data indicate that for those GM crops currently available, WF toxicity studies have been an unnecessary component in the assessment of their safety, yielding no results not predicted from other analyses, with essentially 100% concordance with the predictions based on agronomic and compositional analyses.

“The considerable available data indicate that for those GM crops currently available, WF toxicity studies have been an unnecessary component in the assessment of their safety, yielding no results not predicted from other analyses, with essentially 100% concordance with the predictions based on agronomic and compositional analyses.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

All biological studies are inherently noisy to varying degrees due to environmental and individual variation.

“All biological studies are inherently “noisy” to varying degrees.”

May combine two claims.

For a whole GM food, neither dose ranging nor attainment of an MTD is possible.

“For a whole GM food, neither dose ranging nor attainment of an MTD is possible.”

• AssumptionRests on an assumption: In WF toxicity studies, the test substance(s) are unknown substances that may or may not be present and may or may not be of toxicological significance, and the whole food itself is simply a carrier for any unknown.

Probably not a substantial claim: may not pass S4 (based).

The limitations associated with the use of WF as a test material would be expected to apply equally to lifetime studies and reproduction studies.

“For the purpose of the present review, the limitations associated with the use of WF as a test material would be expected to apply equally to lifetime studies and reproduction studies and these studies will not be considered in depth here.”

Classified as probably not a substantial claim. May combine two claims.

Changes attributed to GM maize were neither sex- nor dose-related and were primarily due to chance alone.

“It was concluded that changes attributed to GM maize were neither sex- nor dose-related and were primarily due to chance alone (EFSA, 2009a; FSANZ, 2011).”

• cites EFSA, 2009aNot checked yet

  Not checked in the free run.

• cites FSANZ, 2011Not checked yet

  Not checked in the free run.

May combine two claims.

If statistical significance is set at p ≤ 0.05, on average 1 parameter in 20 is expected to be statistically significantly different between treatment groups purely by chance, and a few may show evidence of a dose relationship by chance.

“If statistical significance is set at the standard default value of p ≤ 0.05, then on average 1 parameter in 20 (i.e. 5%) is expected to be statistically significantly different between treatment groups purely by chance, and a few of these might even be expected to show evidence of a dose relationship, again purely by chance (McDonald, 2009).”

• cites McDonald, 2009Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The core objective when designing animal studies is maximization of the treatment signal so that it is readily distinguishable from background biological noise in studies utilizing relatively small group sizes.

“The core objective when designing animal studies is the maximization of the treatment “signal” so that it is readily distinguishable from background biological “noise” in studies utilizing relatively small group sizes.”

May combine two claims.

Studies in only one species are a weak basis for extrapolation to humans because an absence of effects in one species does not mean that effects will not be seen in another species.

“Equally, studies in only one species are a weak basis for extrapolation to humans because an absence of effects in one species does not mean that effects will not be seen in another species.”

May combine two claims.

Statistical challenges related to multiple comparisons and a lack of toxicological power are not generally applicable to livestock and poultry feeding studies.

“Furthermore, since the parameters of interest are largely confined to those related to normal growth and development, statistical challenges related to multiple comparisons and a lack of toxicological power are not generally applicable.”

May combine two claims.

In reviewing re-analyses of MON863 data, it was concluded that the incidence of statistically significant differences in animals fed GM corn was entirely consistent with normal background variability, and there was a lack of concordance with other investigative processes.

“In reviewing the re-analyses, it was concluded that the incidence of statistically significant differences in animals fed GM corn (MON863) was entirely consistent with normal background variability, and that there was a lack of concordance of the statistics with other investigative processes used in the studies such as pathology, histopathology, and histochemistry.”

• cites EFSA, 2009aNot checked yet

  Not checked in the free run.

• cites FSANZ, 2011Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

This will be a particular issue where marked treatment-related effects are unlikely and/or implausible, such as with WF toxicity studies.

“This will be a particular issue where marked treatment-related effects are unlikely and/or implausible, such as with WF toxicity studies.”

May combine two claims.

In WF toxicity studies, test substances are unknown and meaningful dose escalation is not achievable.

“This approach, however, is not possible in WF toxicity studies in which the test substance(s) are unknown and meaningful dose escalation is not achievable.”

• AssumptionRests on an assumption: In WF toxicity studies, the test substance(s) are unknown substances that may or may not be present and may or may not be of toxicological significance, and the whole food itself is simply a carrier for any unknown.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

A well-designed toxicology study will include multiple endpoints indicative of biological effect on a single organ or tissue.

“A well-designed toxicology study will include multiple endpoints indicative of biological effect on a single organ or tissue.”

May combine two claims.

The European Society of Toxicologic Pathology described egregious errors of design, conduct, and interpretation in the Séralini et al. (2012) study, expressed shock at the treatment of the animals, and questioned the legality of the study conduct under European law.

“In describing the egregious errors of design, conduct, and interpretation of the study by these authors, the European Society of Toxicologic Pathology expressed shock at the treatment of the animals and questioned the legality of the study conduct under European law (Schorsch et al., 2013).”

• cites Schorsch et al., 2013 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Given the general comparability of GM to non-GM food observed to date, safety testing of GM foods and food constituents is unlikely to lead to unacceptable pain and/or suffering in experimental animals, other than as a result of normal experimental and investigative practices, provided researchers adhere to normal humane practices.

“Given the general comparability of GM to non-GM food observed to date, safety testing of GM foods and food constituents is unlikely to lead to unacceptable pain and/or suffering in the experimental animals used, other than as a result of normal experimental and investigative practices, and provided that the researchers conducting the experiments adhere to normal humane practices.”

• AssumptionRests on an assumption: GM food is generally comparable to non-GM food, as observed to date.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

For compounds of low toxicity, very high or limit doses may be used; if such doses do not produce toxicity, this supports the conclusion that adverse effects in humans are not likely, provided species differences in toxicokinetics do not preclude extrapolation.

“For compounds of low toxicity, very high, or “limit”, doses, hundreds or thousands of times greater than presumptive human exposure levels, may be used. Where such doses do not produce evidence of toxicity in the experimental animals this is taken to provide further support for the conclusion that adverse effects in humans are not likely, provided species differences in toxicokinetics do not precl”

Classified as probably not a substantial claim. May combine two claims.

Electron microscopy of selected tissues may be useful in studies designed to elucidate a chemical's mechanism of action, but it is not a recommended approach in OECD testing guidelines because the relatively small amount of tissue evaluated cannot be considered representative.

“These authors further observed that electron microscopy of selected tissues may be useful in studies designed to elucidate a chemical’s mechanism of action, but it is not a recommended approach in OECD testing guidelines because the relatively small amount of tissue evaluated cannot be considered representative (Williams & DeSesso, 2010).”

• cites Williams & DeSesso, 2010Not checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Some jurisdictions are likely to continue to maintain a requirement for the conduct of WF toxicity studies.

“Regardless of the scientific merits of WF toxicity studies, some jurisdictions are likely to continue to maintain a requirement for their conduct.”

May combine two claims.

WF toxicity studies are essentially bioassays and are inherently less sensitive than the range of analytical chemistry techniques.

“WF toxicity studies are essentially bioassays and are inherently less sensitive than the range of analytical chemistry techniques.”

Classified as probably not a substantial claim. May combine two claims.

Although the limitations of WF toxicity studies cannot be readily eliminated, some strategies are available to somewhat mitigate their impact.

“Although these limitations cannot be readily eliminated, some strategies are available to somewhat mitigate their impact.”

May combine two claims.

In WF toxicity studies, a negative result is un-interpretable because the investigator cannot determine whether the animals were exposed orally or systemically to a test substance not in the control feed, nor consider the likely toxicokinetics or toxicodynamics of any test substance that might be present.

“In such circumstances, a negative result is un-interpretable because the investigator cannot determine whether the animals were actually exposed orally or systemically to a test substance not in the control feed; nor can they consider the likely toxicokinetics or toxicodynamics of any test substance that might be present.”

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

A WF toxicity study is a poor analytical tool and therefore should be considered at best a last resort rather than a normal aspect of GM food safety assessment.

“A WF toxicity study is a poor analytical tool and therefore should be considered at best a last resort rather than a normal aspect of GM food safety assessment.”

May combine two claims.

Range-finding studies for WF toxicity studies, if conducted, are likely to be negative and provide no basis for dose selection.

“Range finding studies, if conducted at all, are likely to be negative and so no basis for dose selection is available.”

May combine two claims.

In WF toxicity studies, the study designer has no knowledge of the nature of the test substance or whether a test substance is present, and lacks knowledge of potential target organs and systems.

“The study designer has no knowledge of the nature of the test substance or even if a test substance is actually present, in addition to a lack of knowledge of potential target organs and systems.”

May combine two claims.

Studies on WFs are of questionable relevance to normal patterns of human consumption, and theoretical margins of exposure based on the whole food are unlikely to be relevant to any specific 'unknown,' especially where that substance may be isolated to one specific fraction of the whole food.

“Consequently, studies on WFs are of questionable relevance to normal patterns of human consumption and theoretical margins of exposure based on the whole food are unlikely to be relevant to any specific “unknown,” especially where that substance may be isolated to one specific fraction of the whole food.”

• AssumptionRests on an assumption: With the exception of fruits and some vegetables, humans generally do not consume raw WFs as such.
• AssumptionRests on an assumption: More commonly, humans consume specific crop components, such as tofu or oil prepared from soybeans.

May combine two claims.

It presents a considerable challenge to identify circumstances under which the conduct of a WF study is scientifically and ethically justified, taking into account the negligible probability that the use of recombinant DNA technology to produce a GM crop will randomly produce novel, unintended toxic substances de novo, the implausibility of any such substances being highly toxic, the low浓度 of

“Thus, it presents a considerable challenge to identify circumstances under which the conduct of a WF study is scientifically and ethically justified, taking into account the negligible probability that the use of recombinant DNA technology to produce a GM crop will randomly produce novel, unintended toxic substances de novo, the implausibility of any such substances being highly toxic, the low”

Probably not a substantial claim: may not pass S3 (load-bearing).

The EFSA scientific opinion on the risk assessment of GM crops places substantial emphasis on the use of WF toxicity studies as a key component of risk assessment.

“The EFSA scientific opinion on the risk assessment of GM crops, for example, places substantial emphasis on the use of WF toxicity studies as a key component of risk assessment.”

• cites EFSA, 2008aNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Removal of a significant proportion of well-characterized components (e.g. starch, oil), removal of components not normally consumed by humans, and processing in a manner consistent with normal food preparation practices before testing will reduce the bulk of the WF, permit higher exposures, and ensure that the test material is consistent with that actually consumed by humans.

“Removal of a significant proportion of well characterized components (e.g. starch, oil), removal of components not normally consumed by humans, and processing in a manner consistent with normal food preparation practices before testing will reduce the bulk of the WF, permitting higher exposures, and ensure that the test material is consistent with that actually consumed by humans.”

• AssumptionRests on an assumption: The bulk of the composition of GM crops is well characterized.

Probably not a substantial claim: may not pass S2 (checkable).

Use of a less sensitive experimental animal method to provide reassurance of the accuracy of more sensitive analytical methods is difficult to justify scientifically or ethically.

“Use of a less sensitive experimental animal method to provide reassurance of the accuracy of more sensitive analytical methods is difficult to justify scientifically or ethically.”

May combine two claims.

The potential for upregulation or alteration of genes responsible for the production of endogenous toxins naturally present in crops such as potatoes is somewhat less tenuous but of equal concern with conventional breeding; these are not de novo hazards arising spontaneously.

“The potential for upregulation or alteration of genes responsible for the production of endogenous toxins naturally present in crops such as potatoes is somewhat less tenuous but of equal concern with conventional breeding; these however, are not de novo hazards arising spontaneously.”

Probably not a substantial claim: may not pass S4 (based).

The protracted animal testing of multiple combinations of food and irradiation dose, despite clear evidence of a lack of need and utility of such studies, provides a close parallel to the current situation with data requirements for GM crops in some jurisdictions.

“The protracted animal testing of multiple combinations of food and irradiation dose, despite clear evidence of a lack of need, and utility of, such studies provides a close parallel to the current situation with data requirements for GM crops in some jurisdictions.”

May combine two claims.

Such possibilities can be readily examined using sensitive analytical techniques and are used in plant breeding to monitor levels of naturally occurring toxins that are identified in OECD consensus documents for specific crops.

“Fortunately such possibilities can be readily examined using sensitive analytical techniques and are used in plant breeding to monitor levels of naturally occurring toxins that are identified in OECD consensus documents for specific crops (Steiner et al., 2013).”

• cites Steiner et al., 2013 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

A review of more than 139 projects conducted by the European Commission over the past 25 years, involving more than 500 independent research groups and representing European research grants of more than €200 million, concluded that biotechnology, and in particular GM organisms, are not more risky per se than conventional plant breeding technologies.

“in which the conclusion of all of that research was that “biotechnology, and in particular [GM Organisms], are not more risky per se than e.g. conventional plant breeding technologies” (European Commission, 2010b).”

• cites European Commission, 2010bNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

The studies in Table 5 highlight the importance of understanding the design challenges and inherent limitations of WF toxicity studies.

“The studies in Table 5 are informative because they highlight the importance of understanding the design challenges and inherent limitations of WF toxicity studies.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

Even in well-designed studies, the evaluation of subtle effects at low doses is a challenge for which adherence to scientific principles and practical experience in this arena is an absolute necessity for proper scientific interpretation.

“Even in well-designed studies, represented by many in Table 4, the evaluation of subtle effects at low doses is a challenge for which adherence to scientific principles and practical experience in this arena is an absolute necessity for proper scientific interpretation.”

May combine two claims.

WF toxicity studies have limited sensitivity to detect low levels of toxicologically significant components in whole food and do not provide additional reassurance of GM food safety beyond that which is already provided by more sensitive, reliable, and robust techniques such as comparative molecular, agronomic, and compositional analyses.

“it is equally arguable that WF toxicity studies have limited sensitivity to detect low levels of toxicologically significant components in whole food and do not provide additional reassurance of GM food safety beyond that which is already provided by more sensitive, reliable, and robust techniques such as comparative molecular, agronomic, and compositional analyses.”

May combine two claims.

Although it has been possible to demonstrate alteration in food composition in animal studies in which a sensitive animal model is available that specifically relates to the depleted vitamin, chemical analytical methods have been shown to be more sensitive and reliable in each case.

“Although it has been possible to demonstrate alteration in food composition in animal studies in which a sensitive animal model is available that specifically relates to the depleted vitamin (e.g. cats and vitamin A), chemical analytical methods have been shown to be more sensitive and reliable in each case.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

This outcome was predictable based on nearly a century of experience of WF toxicity studies on irradiated food involving tens of thousands of experimental animals of multiple species.

“This outcome was predictable based on nearly a century of experience of WF toxicity studies on irradiated food involving tens of thousands of experimental animals of multiple species.”

Classified as probably not a substantial claim. May combine two claims.

The joint FAO/IAEA/WHO review concluded that the application of 'risk assessment' in the currently accepted sense is not appropriate to the toxicological assessment of foods preserved by high-dose irradiation, and that the concept of 'substantial equivalence' may be more appropriate.

“The application of “risk assessment” in the currently accepted sense is not appropriate to the toxicological assessment of foods preserved by high-dose irradiation. In this context, the concept of “substantial equivalence” may be more appropriate.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.

May combine two claims.

The requirement for relatively extensive safety evaluation and WF animal toxicity studies is disproportionate to the known risks and is discordant with the extensive data available.

“In this context, the requirement for relatively extensive safety evaluation and WF animal toxicity studies is disproportionate to the known risks and is discordant with the extensive data available.”

May combine two claims.

Food irradiation is known to produce unintended compositional changes, albeit at low concentrations, and most particularly to reduce the levels of some micronutrients that are vulnerable to attack by free radicals produced by radiolysis of water and other cellular constituents.

“Food irradiation is known to produce unintended compositional changes, albeit at low concentrations, and most particularly to reduce the levels of some micronutrients that are vulnerable to attack by free radicals produced by radiolysis of water and other cellular constituents.”

• cites WHO, 1999Not checked yet

  Not checked in the free run.