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Risk Assessment Bovine Somatotrophin - BST
Case Study
Jim Moynagh
European Commission
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• 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
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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
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Effect of BST on milk yield
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Changes to milk yield and composition
• Yield 0% to 25% - 12% typical
• milk composition - changes seen but within normal variation over lactation
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Changes to milk compositionfollowing single injection
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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
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Organisation
• Human Health
• Animal Health
• General examination of substance
• NOT examination of product dossier
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Types of assessment
• Qualitative
• Quantitative
• Qualitative approach adopted
• (NB quantitative approach adopted concurrently by Canada with similar results)
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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
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Sources used
• Published papers in peer reviewed journals
• Material from Company submissions
With considerable caution;
• Non peer reviewed published material
• Personal communications
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Assessing papers
• Was the experiment statistically robust enough to detect the effect?
• Was the effect reported researched in detail?
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Assessing papers
• Was the experiment statistically robust enough to detect the effect?
Meta-analysis.
• Was the effect reported researched in detail?
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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.
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Animal Health - Issues?
• Increase in mastitis levels
• Increase in foot problems
• Fertility / reproductive problems
• Injection site reactions
• Heat tolerance, burnout etc.
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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
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Outcome - Animal health
• Mastitis
• Foot problems
• Reproductive problems
• Site reactions
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Outcome - Animal health
• Mastitis definite increase (c. 25%)
• Foot problems
• Reproductive problems
• Site reactions
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Outcome - Animal health
• Mastitis
• Foot problems increase in older cows
( x 2.1)
• Reproductive problems
• Site reactions
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Outcome - Animal health
• Mastitis
• Foot problems
• Reproductive problems variable
• Site reactions
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Outcome - Animal health
• Mastitis
• Foot problems
• Reproductive problems
• Site reactions reported
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Outcome - Animal health
• Mastitis definite increase (c. 25%)
• Foot problems increase in older cows
( x 2.1)
• Reproductive problems variable
• Site reactions reported
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Possible reasons for effects
• Part of being a high yielding cow?
• Negative energy and protein balance too prolonged?
• Direct effect of BST?
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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
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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
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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.
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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
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• 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
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• 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
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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?
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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
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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
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Summary - Animal Health
• BST administration results in adverse health effects in the treated animal.
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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?
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Action of policy makers
• ANIMAL HEALTH
• Administration of BST in the European Union was prohibited
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Action of policy makers
• PUBLIC HEALTH
• Precautionary Principle utilised
• No trade measures taken but,
Scientific evidence being kept under review
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Web Site
http://europa.eu.int/comm/dg24/index.html