CoChat
Sign Up
Cited by 230Genetically Modified Organisms ResearchAgricultural safety and regulationsCarcinogens and Genotoxicity Assessment

The DOI matches its Crossref record; 157 of the 162 references it cites were found in a registry or an index.

Safety and nutritional assessment of GM plants and derived food and feed: The role of animal feeding trials

Open access
Report of the EFSA GMO Panel Working Group on Animal Feeding Trials·2008·Food and Chemical Toxicology
DOI 10.1016/j.fct.2008.02.008
Open this paper in CoChat — free account

Abstract

In this report the various elements of the safety and nutritional assessment procedure for genetically modified (GM) plant derived food and feed are discussed, in particular the potential and limitations of animal feeding trials for the safety and nutritional testing of whole GM food and feed. The general principles for the risk assessment of GM plants and derived food and feed are followed, as described in the EFSA guidance document of the EFSA Scientific Panel on Genetically Modified Organisms. In Section 1 the mandate, scope and general principles for risk assessment of GM plant derived food and feed are discussed. Products under consideration are food and feed derived from GM plants, such as maize, soybeans, oilseed rape and cotton, modified through the introduction of one or more genes coding for agronomic input traits like herbicide tolerance and/or insect resistance. Furthermore GM plant derived food and feed, which have been obtained through extensive genetic modifications targeted at specific alterations of metabolic pathways leading to improved nutritional and/or health characteristics, such as rice containing beta-carotene, soybeans with enhanced oleic acid content, or tomato with increased concentration of flavonoids, are considered. The safety assessment of GM plants and derived food and feed follows a comparative approach, i.e. the food and feed are compared with their non-GM counterparts in order to identify intended and unintended (unexpected) differences which subsequently are assessed with respect to their potential impact on the environment, safety for humans and animals, and nutritional quality. Key elements of the assessment procedure are the molecular, compositional, phenotypic and agronomic analysis in order to identify similarities and differences between the GM plant and its near isogenic counterpart. The safety assessment is focussed on (i) the presence and characteristics of newly expressed proteins and other new constituents and possible changes in the level of natural constituents beyond normal variation, and on the characteristics of the GM food and feed, and (ii) the possible occurrence of unintended (unexpected) effects in GM plants due to genetic modification. In order to identify these effects a comparative phenotypic and molecular analysis of the GM plant and its near isogenic counterpart is carried out, in parallel with a targeted analysis of single specific compounds, which represent important metabolic pathways in the plant like macro and micro nutrients, known anti-nutrients and toxins. Significant differences may be indicative of the occurrence of unintended effects, which require further investigation. Section 2 provides an overview of studies performed for the safety and nutritional assessment of whole food and feed. Extensive experience has been built up in recent decades from the safety and nutritional testing in animals of irradiated foods, novel foods and fruit and vegetables. These approaches are also relevant for the safety and nutritional testing of whole GM food and feed. Many feeding trials have been reported in which GM foods like maize, potatoes, rice, soybeans and tomatoes have been fed to rats or mice for prolonged periods, and parameters such as body weight, feed consumption, blood chemistry, organ weights, histopathology etc have been measured. The food and feed under investigation were derived from GM plants with improved agronomic characteristics like herbicide tolerance and/or insect resistance. The majority of these experiments did not indicate clinical effects or histopathological abnormalities in organs or tissues of exposed animals. In some cases adverse effects were noted, which were difficult to interpret due to shortcomings in the studies. Many studies have also been carried out with feed derived from GM plants with agronomic input traits in target animal species to assess the nutritive value of the feed and their performance potential. Studies in sheep, pigs, broilers, lactating dairy cows, and fish, comparing the in vivo bioavailability of nutrients from a range of GM plants with their near isogenic counterpart and commercial varieties, showed that they were comparable with those for near isogenic non-GM lines and commercial varieties. In Section 3 toxicological in vivo, in silico, and in vitro test methods are discussed which may be applied for the safety and nutritional assessment of specific compounds present in food and feed or of whole food and feed derived from GM plants. Moreover the purpose, potential and limitations of the 90-day rodent feeding trial for the safety and nutritional testing of whole food and feed have been examined. Methods for single and repeated dose toxicity testing, reproductive and developmental toxicity testing and immunotoxicity testing, as described in OECD guideline tests for single well-defined chemicals are discussed and considered to be adequate for the safety testing of single substances including new products in GM food and feed. Various in silico and in vitro methods may contribute to the safety assessment of GM plant derived food and feed and components thereof, like (i) in silico searches for sequence homology and/or structural similarity of novel proteins or their degradation products to known toxic or allergenic proteins, (ii) simulated gastric and intestinal fluids in order to study the digestive stability of newly expressed proteins and in vitro systems for analysis of the stability of the novel protein under heat or other processing conditions, and (iii) in vitro genotoxicity test methods that screen for point mutations, chromosomal aberrations and DNA damage/repair. The current performance of the safety assessment of whole foods is mainly based on the protocols for low-molecular-weight chemicals such as pharmaceuticals, industrial chemicals, pesticides, food additives and contaminants. However without adaptation, these protocols have limitations for testing of whole food and feed. This primarily results from the fact that defined single substances can be dosed to laboratory animals at very large multiples of the expected human exposure, thus giving a large margin of safety. In contrast foodstuffs are bulky, lead to satiation and can only be included in the diet at much lower multiples of expected human intakes. When testing whole foods, the possible highest concentration of the GM food and feed in the laboratory animal diet may be limited because of nutritional imbalance of the diet, or by the presence of compounds with a known toxicological profile. The aim of the 90-days rodent feeding study with the whole GM food and feed is to assess potential unintended effects of toxicological and/or nutritional relevance and to establish whether the GM food and feed is as safe and nutritious as its traditional comparator rather than determining qualitative and quantitative intrinsic toxicity of defined food constituents. The design of the study should be adapted from the OECD 90-day rodent toxicity study. The precise study design has to take into account the nature of the food and feed and the characteristics of the new trait(s) and their intended role in the GM food and feed. A 90-day animal feeding trial has a large capacity (sensitivity and specificity) to detect potential toxicological effects of single well defined compounds. This can be concluded from data reported on the toxicology of a wide range of industrial chemicals, pharmaceuticals, food substances, environmental, and agricultural chemicals. It is possible to model the sensitivity of the rat subchronic feeding study for the detection of hypothetically increased amount of compounds such as anti-nutrients, toxicants or secondary metabolites. With respect to the detection of potential unintended effects in whole GM food and feed, it is unlikely that substances present in small amounts and with a low toxic potential will result in any observable (unintended) effects in a 90-day rodent feeding study, as they would be below the no-observed-effect-level and thus of unlikely impact to human health at normal intake levels. Laboratory animal feeding studies of 90-days duration appear to be sufficient to pick up adverse effects of diverse compounds that would also give adverse effects after chronic exposure. This conclusion is based on literature data from studies investigating whether toxicological effects are adequately identified in 3-month subchronic studies in rodents, by comparing findings at 3 and 24 months for a range of different chemicals. The 90-day rodent feeding study is not designed to detect effects on reproduction or development other than effects on adult reproductive organ weights and histopathology. Analyses of available data indicate that, for a wide range of substances, reproductive and developmental effects are not potentially more sensitive endpoints than those examined in subchronic toxicity tests. Should there be structural alerts for reproductive/developmental effects or other indications from data available on a GM food and feed, then these tests should be considered. By relating the estimated daily intake, or theoretical maximum daily intake per capita for a given whole food (or the sum of its individual commercial constituents) to that consumed on average per rat per day in the subchronic 90-day feeding study, it is possible to establish the margin of exposure (safety margin) for consumers. Results obtained from testing GM food and feed in rodents indicate that large (at least 100-fold) 'safety' margins exist between animal exposure levels without observed adverse effects and estimated human daily intake. Results of feeding studies with feed derived from GM plants with improved agronomic properties, carried out in a wide range of livestock species, are discussed. The studies did not show any biologically relevant differences in the parameters tested between control and test animals. (ABSTRACT TRUNCATED)

Overview

Integrity signals

Registry

Crossref · 10.1016/j.fct.2008.02.008

Cites

157 of 157 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 71

  1. Aalhus, 2003, Effects of feeding glyphosat-tolerant canola meal on swine growth, carcass composition and meat quality, J. Anim. Sci., 81, 3267
  2. Aeschbacher, 2001, Physiological characteristics of Bt 176-corn in poultry and destiny of recombinant plant DNA in poultry products, Ann. Nutr. Metab., 45, 376
  3. Berger, 2002, Effect of feeding diets containing corn grain with Roundup (event GA21 or NK603), control, or conventional varieties on steer feedlot performance and carcass characteristics, J. Anim. Sci., 80, 270
  4. Berger, 2003, Effect of feeding diets containing corn grain with corn rootworm protection (event MON 863), control, or conventional varieties on steer feedlot performance and carcass characteristics, J. Anim. Sci., 81, 214
  5. Bertrand, 2002, Comparison of nutrient content and digestibility of traditional versus genetically modified whole cottonseed, J. Dairy Sci., 85, 119
  6. Bressner, 2002, A comparison of swine performance when fed diets containing Roundup Ready (event NK603) or conventional corn lines, J. Anim. Sci., 80, 63
  7. Bressner, 2003, Performance comparison of growing-finishing pigs fed diets containing Corn Root Worm Protected corn (Event MON 863) or conventional corn hybrids, J. Anim. Sci., 81, 207
  8. Casarett & Doull’s Toxicology, 2001. The Basic Science of Poisons. Curtis D. Klaassen. McGraw-Hill Medical Publisher, 1236 p.
  9. Centres for Disease Control and Prevention, 2001. Investigation of Human Health Effects Associated with Potential Exposure to Genetically Modified Corn, pp. 1–24.
  10. Chrastinova, 2002, Genetically modified maize in diets for rabbits – influence on performance and product quality, Proc. Soc. Nutr. Physiol., 11, 195
  11. Cromwell, 2004, Herbicide-tolerant rice versus conventional rice in diets for growing-finishing pigs, J. Anim. Sci., 82, 329
  12. Custodio, 2004, Growth and carcass characteristics of pigs fed biotechnologically derived and non-biotechnologically derived corn and harvested at different weights, J. Anim. Sci., 82, 456
  13. Daenicke, 1999, GVO in der Fütterung, Mais, 27, 135
  14. Donkin, 2000, Effect of feeding Roundup Ready corn silage and grain on feed intake, milk production and milk composition in lactating dairy cattle, J. Anim. Sci., 78, 273
  15. EC, 1997, Off. J. Eur. Communities. L, 253, 1
  16. EC, 1997, Regulation (EC) No 258/97 of the European Parliament and of the Council of 27 January 1997 concerning novel food and novel food ingredients, Off. J. Eur. Communities, L43, 1
  17. EC, 2000, Off. J. Eur. Communities, L200, 59
  18. EC, 2004, Off. J. Eur. Communities, L, 50, 44
  19. EFSA, 2004, EFSA J., 50, 1
  20. EFSA, 2004, EFSA J., 49, 1
  21. EFSA, 2005, EFSA J., 251, 1
  22. EFSA, 2005, EFSA J., 252, 1
  23. EFSA, 2005, EFSA J., 182, 1
  24. EFSA, 2005, EFSA J., 181, 1
  25. EFSA, 2006, Guidance document of the Scientific Panel on Genetically Modified Organisms for the risk assessment of genetically modified plants and derived food and feed, EFSA J., 99, 1
  26. EFSA, 2006, Guidance document of the Scientific Panel on genetically modified organisms for the risk assessment of genetically modified microorganisms and their derived products intended for food and feed use, EFSA J., 374, 1
  27. EFSA, 2007, EFSA J., 470, 1
  28. EFSA, 2007, Guidance document of the Scientific Panel on genetically modified organisms for the risk assessment of genetically modified plants containing stacked transformation events, EFSA J., 512, 1
  29. Elliott, 2003, Surveillance and post-market monitoring of potential health effects of novel (including GM) foods, Feasibility Study, 1
  30. ENTRANSFOOD, 2004, Safety assessment, detection and traceability and societal aspects of GM foods, Food Chem. Toxicol., 42, 1069
  31. Fischer, 2002, Comparison of swine performance when fed diets containing Roundup Ready corn (event NK 2003), control, or conventional corn grown during 2000 in Nebraska, J. Anim. Sci., 80, 224
  32. Fischer, 2003, Comparison of swine performance when fed diets containing corn root worm protected corn, parental line corn, or conventional corn grown during 2000 in Nebraska, J. Anim. Sci., 81, 207
  33. FOSIE, 2002, Food safety in Europe: risk assessment of chemicals in food and diet, Food Chem. Toxicol., 40, 137
  34. Gad, 1994, Statistics for Toxicologist, Principles Methods Toxicol., 221
  35. Gaines, 2001, Nutritional evaluation of Bt (MON 810) and Roundup Ready® corn compared with commercial hybrids in broilers, Poult. Sci., 80, 51
  36. Gaines, 2001, Swine digestible energy evaluations of Bt (MON 810) and Roundup Ready corn compared with commercial varieties, J. Anim. Sci., 79, 109
  37. GM Science Review Panel, 2003. GM Science Review. First Report 6704/0. Department of Trade and Industry, London, pp. 92–96. <http://www.gmsciencedebate.org.uk/report/pdf/gmsci-report1-full.pdf>.
  38. GM Science Review Panel, 2004. GM Science Review. Second Report. Department of Trade and Industry, London, pp. 60–61. <http://www.gmsciencedebate.org.uk/report/pdf/gmsci-report2-full.pdf>.
  39. Halle, I., Aulrich K., Flachowsky, G., 1999. Einstaz von Maiskornern der Sorte Cesar und des gentechnisch veranderten Bt-hybriden in der Broilermast. In: Proceedings of the 5 Tagung, Schweine und Geflügelernährung. Wittenberg, Germany, pp. 265–271.
  40. Halle, 2006, Four generations feeding GMO-corn to laying hens, Proc. Soc. Nutr. Physiol., 15, 114
  41. IARC Handbooks of Cancer Prevention, 2003, Fruit and Vegetables, 8, 272
  42. ILSI, 2006. Crop Composition Database. Version 3.0. ©2003, 2004, 2006 International Life Sciences Institute. <http://www.cropcomposition.org>.
  43. Kerley, 2001, Bt corn that is genetically modified to prevent insect damage is equal to conventional corn in feeding value for beef cattle, J. Anim. Sci., 79, 98
  44. Li, 2002, Common gene targets of Ginkgo biloba extract (EGb 761) in human tumor cells: relation to cell growth, Cell Mol. Biol., 48, 655
  45. Maertens, 1996, Digestibility of non-transgenic and transgenic oilseed rape in rabbits, Proceedings of the Sixth World Rabbit Congress, Toulouse, vol. 1, 231
  46. Mireles, 2000, GMO (Bt) corn is similar in composition and nutrient availability to broiler as non-GMO corn, Poultry Sci., 79, 65
  47. Noteborn, H.P.J.M., Kuiper, H.A., 1994. Safety assessment strategies for genetically modified plant products. Case study: Bacillus thuringiensis-toxin tomato. In: Jones, D.D. (Eds.), Proceedings of the Third International Symposium on the Biosafety Results of Field Tests of Genetically Modified Plants and Microorganisms. University of California, Division of Agriculture and Natural Resources, Oakland, CA , pp. 199–207.
  48. OECD, 1997. Report of the OECD Workshop on the Toxicology and Nutritional Testing of Novel Foods, Aussois, France, 5–8 March 1997, OECD, Paris.
  49. OECD, 2002d. Report of the OECD workshop on nutritional assessment of novel food and feed, 5–7 February 2001. Ottawa, Canada. Organization for Economic Co-operation and Development (OECD), Paris.
  50. Peterson, 2003, A comparison of swine performance when fed diets containing Roundup Ready® wheat (event MON 71800) and conventional wheat varieties, J. Anim. Sci., 81, 207
  51. Petty, 2001, Feeding value of Bt corn grain compared with its parental hybrid when fed in beef cattle finishing diets, J. Anim. Sci., 79, 102
  52. Petty, 2001, Performance of beef cattle fed Roundup Ready corn harvested as whole plant silage or grain, J. Anim. Sci., 79, 102
  53. Piva, 2001, Performance of weaned piglets fed insect-protected (MON 810) or near isogenic corn, J. Anim. Sci., 79, 106
  54. Piva, 2001, Growth performance of broilers fed insect-protected (MON 810) or near isogenic control corn, Poultry Sci., 80, 320
  55. Querubin, 2004, Feeding value of two yieldgard corn hybrids versus their isogenic counterparts, treated with and without insecticides, in broiler diets, In: Proceedings of the 11th AAAP Congress 2004, vol. 1, 111
  56. Royal Society, 1999. Review of Data on Possible Toxicity of GM Potatoes (Ref. 11/99). The Royal Society, London. <http://royalsociety.org/displaypagedoc.asp?id=6170>.
  57. SCF, 1991. Guidelines for the presentation of data on food enzymes (opinion expressed on 11 April 1991). Reports of the Scientific Committee for Food: Twenty-Seventh Series, 1992, Catalogue No EUR 14181, pp. 13–22.
  58. Scientific Advisory Committee on Nutrition, 2005. Review of Dietary Advice on Vitamin A. TSO, London, pp. 1–82.
  59. Stanisiewski, 2001, Comparison of swine performance when fed diets containing Roundup Ready corn (GA21), parental line or conventional corn, J. Anim. Sci., 79, 319
  60. Stanisiewski, 2002, Broiler performance when fed RR (event RT 73) or conventional canola meal, Poultry Sci., 81, 95
  61. Stein, 2004, Comparison of corn grain from biotech and non-biotech counterparts for grow-finish pig performance, J. Anim. Sci., 82, 328
  62. Su, 2006, Crude extract of garlic induced caspase-3 gene expression leading to apoptosis in human colon cancer cells, In Vivo, 20, 85
  63. Taylor, 2001, Comparison of broiler performance when fed diets containing YieldGard corn, YieldGard and Roundup Ready corn, parental lines, or commercial corn, Poultry Sci., 80, 319
  64. Taylor, 2001, Comparison of broiler performance when fed diets containing Roundup Ready corn event NK603, parental line, or commercial corn, Poultry Sci., 80, 320
  65. Taylor, 2002, Comparison of broiler performance when fed diets containing YieldGard (MON 810)×Roundup Ready (NK603), nontransgenic control, or commercial corn, Poultry Sci., 81, 95
  66. Taylor, 2004, Comparison of broiler performance when fed diets containing insect-protected (MON 88017 or MON 88017×MON 810), control, or commercial corn, Poultry Sci., 83, 322
  67. Taylor, 2004, Comparison of broiler performance when fed diets containing corn with a combination of insect-protected (MON 863, MON 810) and glyphosate-tolerant (NK603) traits, control, and commercial corn, Poultry Sci., 83, 323
  68. Taylor, 2004, Broiler performances and carcass parameters of broiler fed diet containing lysine maize, Poultry Sci., 83, 315
  69. Vecchio, 2004, Ultrastructural analysis of testes from mice fed on genetically modified soybean, Eur. J. Histochem., 48, 448
  70. Weber, 2001, Grower-finisher growth performance and carcass characteristics including attempts to detect transgenic plant DNA and protein in muscle from pigs fed genetically modified “Bt” corn, J. Anim. Sci., 79, 67
  71. WHO, 1995. Application of the principle of substantial equivalence to the safety evaluation of foods or food components from plants derived by modern biotechnology. Report of a WHO Workshop. WHO, Geneva.

Cited by

Sorted by citations

See all 230

Related

See all

Metadata

Authors
Report of the EFSA GMO Panel Working Group on Animal Feeding Trials
Corresponding author
Report of the EFSA GMO Panel Working Group on Animal Feeding Trials
Venue
Food and Chemical Toxicology
Publisher
Elsevier BV
Published
2008-03
Volume
46
Pages
S2-S70
ISSN
0278-6915 (ISSN-L)
DOI
10.1016/j.fct.2008.02.008
OpenAlex
W2109694674
Cited by
230
References
162
Citations by year
2026: 5 · 2025: 5 · 2024: 5 · 2023: 14 · 2022: 17 · 2021: 10 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 18 · 2016: 22 · 2015: 16 · 2014: 15 · 2013: 20 · 2012: 21
FWCI
1.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Food and Chemical Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • Socio-Environmental Systems Modeling (acceptedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
  • Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
  • OpenAgrar (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Genetically Modified Organisms Research
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Agricultural safety and regulations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
transgenic plants, feeding experiments, safety assessment, nutritional assessment, risk assessment, unintended consequences, compositional analysis, antinutritional factors, herbicide tolerance, insect resistance, novel foods, irradiated food, EFSA guidance
MeSH terms
Animals, Animal Feed, Consumer Product Safety, Food Handling, Humans, Nutritive Value, Product Surveillance, Postmarketing, Toxicity Tests, Models, Animal, Plants, Genetically Modified, Food, Genetically Modified

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review