1. Toxicological Assessment Heinz Hofer ARC Seibersdorf research GmbH Department of Toxicology

2. 2 Some results of the dossier evaluations  Extent of the toxicological investigations: no marked differences between 90/220/EEC and 258/97/EC.  An acute oral toxicity study was performed with each newly inserted protein, in most cases.

3. 3 Some further results, 1  Other usually investigated toxicological endpoints, as e.g. repeated dose toxicity, chronic toxicity, genotoxicity, reproduction toxicity, malformations of new-borns or carcinogenicity were not investigated.  No systematic risk assessment was performed (with one exception).

4. 4 Methods of risk assessment First source The application of the principle of Substantial Equivalence was the main method to show a low risk of the GM plant

5. 5 Methods of risk assessment Second source Assumption based reasoning - and not only fact based reasoning - was observed repeatedly, to produce favourable statements.

6. 6 Example for assumption based reasoning "This food has been used commercially for 4 years, and 300 million Americans are currently eating it with no sign of a problem.“ This statement was taken then as an argument for the safety of the GM food.

7. 7 Critique The opinion on lacking toxic effects of the GMP is not the result of extensive toxicological studies, but is an opinion that could arise, when missing results due to missing investigations are misinterpreted as "non-toxic" effects.

8. 8 Critique Opinions like "no signs of a problem" or "long history of safe use" are by no means proofs for safety.

9. 9 From the EU Recommendation 97/618/EC "Thus, foods have not hitherto been systematically subjected to nutritional or toxicological evaluation, except in rare cases,...."

10. 10 Method of risk assessment Third source The digestibility of the new protein was tested in in vitro assays. Digestibility is usually fast, indicating an only low absorption of the protein. Critique: It is the opinion of the Scientific Committee on Plants, that in vivo assays should be performed (and not only in vitro assays).

11. 11 Methods of risk assessment Fourth source The homology of the new protein with known toxins or other protein was checked. Critique: An identity of only ca. 50 % of the amino acid sequence of the new protein with a well known protein, was taken as a “proof” for the low toxicity.

12. 12 Some further results, 3 Underdeveloped regulations and guidance documents on  testing methods,  data requirements,  dossier preparation,  risk assessment,  decisions on authorisation,  quality aspects, compared to other regulated products.

13. 13 Recommendations, 1  To dismiss the principle of substantial equivalence, as it is not ascertained that the conventional counterparts are safe.  Instead of, to require toxicological investigations of the whole GMPs, to cover also other toxicological endpoints, e.g. carcinogenicity. Possible secondary effects could be detected when the whole food plant is investigated.

14. 14 Recommendations, 2  The risk assessment of GM crops should be based on toxicological results and on the estimated exposure.  To create guidance documents on  data requirements  dossier preparation  risk assessment  authorisation  standard formats  standard testing methods  Good Laboratory Practice

15. 15 Recommendation, 3 The updated risk assessment and authorisation procedure of GMPs should be a starting point of the systematical toxicological evaluation of traditional food plants, which is overdue.