Risk Assessment Bovine Somatotrophin - BST

Case Study

Jim Moynagh

European Commission

• 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

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

Effect of BST on milk yield

Changes to milk yield and composition

• Yield 0% to 25% - 12% typical

• milk composition - changes seen but within normal variation over lactation

Changes to milk compositionfollowing single injection

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

Organisation

• Human Health

• Animal Health

• General examination of substance

• NOT examination of product dossier

Types of assessment

• Qualitative

• Quantitative

• Qualitative approach adopted

• (NB quantitative approach adopted concurrently by Canada with similar results)

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

Sources used

• Published papers in peer reviewed journals

• Material from Company submissions

With considerable caution;

• Non peer reviewed published material

• Personal communications

Assessing papers

• Was the experiment statistically robust enough to detect the effect?

• Was the effect reported researched in detail?

Assessing papers

• Was the experiment statistically robust enough to detect the effect?

Meta-analysis.

• Was the effect reported researched in detail?

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.

Animal Health - Issues?

• Increase in mastitis levels

• Increase in foot problems

• Fertility / reproductive problems

• Injection site reactions

• Heat tolerance, burnout etc.

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

Outcome - Animal health

• Mastitis

• Foot problems

• Reproductive problems

• Site reactions

Outcome - Animal health

• Mastitis definite increase (c. 25%)

• Foot problems

• Reproductive problems

• Site reactions

Outcome - Animal health

• Mastitis

• Foot problems increase in older cows

( x 2.1)

• Reproductive problems

• Site reactions

Outcome - Animal health

• Mastitis

• Foot problems

• Reproductive problems variable

• Site reactions

Outcome - Animal health

• Mastitis

• Foot problems

• Reproductive problems

• Site reactions reported

Outcome - Animal health

• Mastitis definite increase (c. 25%)

• Foot problems increase in older cows

( x 2.1)

• Reproductive problems variable

• Site reactions reported

Possible reasons for effects

• Part of being a high yielding cow?

• Negative energy and protein balance too prolonged?

• Direct effect of BST?

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

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

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.

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

• 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

• 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

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?

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

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

Summary - Animal Health

• BST administration results in adverse health effects in the treated animal.

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?

Action of policy makers

• ANIMAL HEALTH

• Administration of BST in the European Union was prohibited

Action of policy makers

• PUBLIC HEALTH

• Precautionary Principle utilised

• No trade measures taken but,

Scientific evidence being kept under review

Web Site

http://europa.eu.int/comm/dg24/index.html