1. Risk Assessment Bovine Somatotrophin - BST Case Study Jim Moynagh European Commission

2. What is BST and what does it do Risk analysis carried out - what and how Analysis of animal health aspects Analysis of public health aspects Risk management decisions taken

3. What is BST? Protein found in pituitary Commercial versions have small amino acid differences Administered to dairy cows by i/m injection every 14 days - 60 days after calving until end of lactation BST acts to increase milk yield BST has no therapeutic use

4. Effect of BST on milk yield

5. Changes to milk yield and composition Yield 0% to 25% - 12% typical milk composition - changes seen but within normal variation over lactation

6. Changes to milk composition following single injection

7. Other Changes Increase in BST secretion in milk Increase in Insulin Growth Factors in milk both naturally found in milk from untreated cows but usually in lesser amounts

8. Organisation Human Health Animal Health General examination of substance NOT examination of product dossier

9. Types of assessment Qualitative Quantitative Qualitative approach adopted (NB quantitative approach adopted concurrently by Canada with similar results)

10. Working Procedures Two Scientific Committees –Public Health –Animal Health and Welfare Established expert working groups to review evidence and prepare report minority reports encouraged Reports extensively referenced and published on web

11. Sources used Published papers in peer reviewed journals Material from Company submissions With considerable caution; Non peer reviewed published material Personal communications

12. Assessing papers Was the experiment statistically robust enough to detect the effect? Was the effect reported researched in detail?

13. Assessing papers Was the experiment statistically robust enough to detect the effect? Meta-analysis. Was the effect reported researched in detail?

14. Assessing papers Was the experiment statistically robust enough to detect the effect? Meta-analysis. Was the effect reported researched in detail? Emphasise results from experiments that specifically measure effect.

15. Animal Health - Issues? Increase in mastitis levels Increase in foot problems Fertility / reproductive problems Injection site reactions Heat tolerance, burnout etc.

16. Public Health - Issues? effects of increased BST in milk Increase in mastitis causing increased use of antibiotics thereby increasing problems of resistance allergic reactions to changes in milk protein composition effects of increased IGF-1 in milk

17. Outcome - Animal health Mastitis Foot problems Reproductive problems Site reactions

18. Outcome - Animal health Mastitis definite increase (c. 25%) Foot problems Reproductive problems Site reactions

19. Outcome - Animal health Mastitis Foot problems increase in older cows ( x 2.1) Reproductive problems Site reactions

20. Outcome - Animal health Mastitis Foot problems Reproductive problems variable Site reactions

21. Outcome - Animal health Mastitis Foot problems Reproductive problems Site reactions reported

22. Outcome - Animal health Mastitis definite increase (c. 25%) Foot problems increase in older cows ( x 2.1) Reproductive problems variable Site reactions reported

23. Possible reasons for effects Part of being a high yielding cow? Negative energy and protein balance too prolonged? Direct effect of BST?

24. Public Health Issues Direct effect of BST in milk Effects of IGF-1 in milk Indirect issues –Increased use of antibiotics increasing risk of resistance developing –change in milk protein composition and allergies

25. Direct effect of BST in milk BST and metabolites rapidly broken down in gastrointestinal tract and by pasteurisation bovine BST does not interact with human GH receptors no evidence for any direct biological effect in humans following oral ingestion

26. Insulin like growth factors (IGFs) IGF-I and IGF-II production in liver stimulated by BST Involved in numerous physiological processes including cellular growth regulation and tumour promotion because of IGF is involved in multiple biological processes, it is not possible to define a dose-effect relationship which describes all individual events.

27. Effects of IGF-1 in milk Bovine IGF-I is identical to human IGF-I though truncated, more active forms occur IGF-1 present in normal milk, increased levels in BST milk (x1.25 - x5) IGF-I is not denatured by pasteurisation

28. IGF-1 survives digestion in combination with casein Intake in milk is much lower than normal secretion into GIT IGF-I may have specific physiological role in the neonate

29. IGF-I increases all intestinal cellular growth parameters and stimulate cell division High normal levels of IGF-1 in humans linked to greater risk of cancer development (cause or marker?) positive correlation between dairy product consumption and breast cancer

30. Need to know…. To what extent can IGF-I in the diet induce any adverse effects on the gastrointestinal tract as a consequence of long term exposure?

31. Secondary Risks RESIDUES BST produces effects by regulating expression of genes including enzymes involved in bio-inactivation and elimination of pharmaceuticals Risk to increase undesirable drug residues

32. Secondary Risks MASTITIS BST Treatment increases the risk of mastitis leading to more use of antibiotics and increased risk of resistance and allergies Policy is to reduce unnecessary use of antibiotics

33. Summary - Animal Health BST administration results in adverse health effects in the treated animal.

34. Summary - Public Health There are grounds for concern concerning the long term effects of increasing the levels of IGF in the gut. Need to determine to what extent can IGF-I in the diet induce any adverse effects as a consequence of long term exposure?

35. Action of policy makers ANIMAL HEALTH Administration of BST in the European Union was prohibited

36. Action of policy makers PUBLIC HEALTH Precautionary Principle utilised No trade measures taken but, Scientific evidence being kept under review

37. Web Site http://europa.eu.int/comm/dg24/index.html