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Bovine somatotropin (bST)
Institute Of Food Science & Technology
September 1999
Summary
[Special Note: Having regard to the current conflict of interpretation
of evidence, this Information Statement represents an IFST overview
of the present position in relation to this topic, and does not
imply that IFST has adopted a position in relation to the continuing
controversy].
The effects of bST treatment of cows in relation to human health
and animal health have been re-evaluated by the Food and Drug Administration
(FDA) in USA, and have been evaluated by independent assessments
for the Canadian authorities, by Codex Alimentarius and by scientific
committees of the European Union.
The US and Canadian assessments both concluded that products from
bST-treated cows present no hazard to human health, and this is
supported by the Codex assessment. However, the EU assessment is
inconclusive, while drawing attention to potential hazards requiring
more research.
The US reassessment reaffirmed that bST treatment is not harmful
to animal health, but both the Canadian and EU assessments concluded
that it is harmful to animal health.
To go straight to Editorial Footnotes describing
subsequent matters of note, use this link.
Background
bST is, confusingly, referred to variously as bST or rbST, or,
rbST or rBGH). Here the term bST is used except where quoting from
the relevant documents, in which case the term used in a particular
document has been retained, and when directly comparing "natural"
bST with recombinant bST.
Somatotropin is a proteinaceous hormone produced by the anterior
pituitary gland situated at the base of the brain. After its discovery
in the 1930's, it was found that rats in the growth phase when injected
with a crude rat pituitary extract underwent increased growth rate.
In the 1950's, it was discovered that certain types of human dwarfism
were due to an inadequate pituitary production of somatotropin.
However, clinical trials involving the injection of these patients
with bST demonstrated that bST was not biologically active in humans.
bST is produced naturally by all cows and has direct and indirect
effects in coordinating the metabolism of various body organs and
tissues to the requirements of milk production, In particular by
promoting production of the hormone IGF-1, which stimulates glands
in the cow's udder. Small quantities of bST are found in all cows'
milk. More recently, high-yielding dairy cows were found to have
higher circulating levels of naturally occurring bST, and it was
discovered that the injection of bST could increase the milk yield
of cows by minimising the rate of yield decline after peak lactation
(bST can only produce a biological effect by injection - the oral
route leads to its breakdown under acidic conditions by proteases
in the digestive system).
The early experiments, many conducted in the UK, were carried out
with bST extracted from the pituitary glands of slaughtered cows,
not a supply suitable for extensive agricultural use. The application
of modern biotechnology has resulted in the development of recombinant
bST (referred to variously as rbST, or, rbST or rBGH), identical
in activity to natural bST. This is done by taking, from the DNA
of cows, the specific gene sequence that carries the instructions
for making bST, and inserting it into E coli, which
can then produce large amounts of recombinant bST.
The amino acid sequence of bST, which gives it its three-dimensional
shape, differs by about 35% from that of human somatotropin (HST)
- the bearing of this on human health is discussed below. bST can
either be 190 or 191 amino acids long; in addition, there can be
either of two different amino acids (leucine or valine) at position
number 126 in the sequence. Thus, four different variants of bST
are produced naturally. rbST may differ slightly, in that a few
extra amino acids may be attached at the N-terminal end of the bST
molecule in the manufacturing process. The additional amino acids
on the end of the protein do not alter its biological activity because
the three-dimensional shape of the active part of the molecule which
binds to the tissue receptors is not changed. They are solely present
as a result of the additional base-pairs on the bST gene which have
been added to aid the bacteria to express the gene in the most efficient
manner during production of rbST. However, they confer on rbST an
increased molecular weight over that of natural bST. Recent developments
in electro-spray mass spectrometry analysis have made it possible
to use the difference in molecular weight to distinguish between
them. This technique has been used to determine the differences
in molecular weight between the natural bST and one of the recombinant
products (Somagrebove®). Purified preparations of bovine pituitary
bST and rbST were used (Scippo et al, 1997).
bST Application
Treatment of cows with bST was approved in February 1994 by the
Food and Drug Administration (FDA) for use in USA , and has been
extensively used over the ensuing period. In addition, regulatory
agencies in 34 countries have reached similar conclusions with respect
to food safety, 24 of which have actually given approval for use
of bST, namely Algeria, Brazil, Bulgaria, Columbia, Costa Rica,
Czech Republic, Honduras, Hungary, Jamaica, Kenya, Korea, Malaysia,
Mexico, Namibia, Pakistan, Peru, Romania, Russia, Slovakia, South
Africa, Turkey, UAE, Ukraine and Zimbabwe.
In use, the product is presented in filled syringes, for subcutaneous
administration, at the tailhead, once every 14 or 28 days to cattle
to increase milk production and improve the efficiency of feed use.
It is normally applied only to certain lower-yielding cows within
a herd, and only during the later period of their lactation, Because
of the bulking of milk from a herd, in such herds segregation of
milk from bST treated cows is impracticable.
At present bST treatment is not permitted in in the European Union
(EU), where there has been a moratorium on its use since 1993, initially
intended to give time to study the situation and prompted mainly
by the regime of milk quotas to avoid over-production. In 1994 the
moratorium was extended to 31 December 1999. If its use were to
be considered in the UK or EU, bST would fall within the legal definition
of a medicinal product, requiring a licence for marketing. Applications
for a licence are considered in the UK by the VPC, the independent
scientific body established under the Act to advise the Health and
Agriculture Ministers on applications for product licences and certificates.
Its members are drawn from various fields of animal and human health,
including veterinary science, toxicology, pharmacology and human
medicine, statistics and environmental sciences. A company applying
for approval of a product is required to provide all relevant scientific
data (including the full range of comparative analyses of milk composition,
toxicological studies, and the results of investigations into how
recombinant bST is metabolised during human digestion) for assessment
by the Committee. Unless these data indicate that the product meets
the licensing criteria of safety, quality and efficacy, the company
is asked to undertake further work if it wishes to proceed with
its application. Safety in this respect also covers the welfare
of treated animals.
In 1993 the EU Committee on Veterinary Medicinal Products (CVMP)
stated that, if permitted, bST should only be available within the
Community on veterinary prescription, and also recommended that
systematic and clearly defined procedures should be established
for the collection and evaluation of any adverse drug reaction reports
associated with the use of the products. Successful use of the product
would require a high quality nutritional regime for treated animals,
good hygiene at the injection site, ongoing monitoring of somatic
cell counts of milk obtained from treated animals, and the inclusion
of detailed instructions for use on product labels and all product-related
literature. These requirements are normal for such products. To
derive the maximum benefits from the use of bST, veterinary advice
would be needed as to the cows to which it should be administered,
the appropriate timing of such administration, and the nutritional
and reproductive management of animals to which it has been administered.
The CVMP considered that appropriate advice should be included on
the packaging stating that bST should not be used on first lactation
heifers and should not be used in other dairy cows until pregnancy
is confirmed. The CVMP concluded that it was important to verify
that the overall level of risk to the health and welfare of the
target animal is not increased when bST is used under commercial
conditions. It therefore recommended that, if licensed, a wide ranging
structured study of at least two years duration should be undertaken
under veterinary supervision to determine the effects of bST on
the incidence of mastitis and associated metabolic disorders under
practical conditions of use. Interim reports would be required to
be presented to Member States and the CVMP at the end of the first
and second years of the study. In addition a structured programme
of adverse reaction reporting should also be established, and consolidated
reports, including information about sales and the number of doses
sold, would be required to be presented to Member States and the
CVMP every six months in the first two years following authorisation,
and annually thereafter until the 5 yearly renewal becomes due.
Suspected adverse reaction reports would include possible effects
on both animals and humans.
Evaluations and Debate
There has been, and continues to be, controversy about the use
of bST, originating with opponents of its approval before and after
its approval by the FDA in the USA in February 1994, but spilling
over into the rest of the world and especially Europe and Canada.
Expressed concerns have centred on four main aspects, human health,
animal health and welfare, labelling and socio-economic aspects.
Objective assessment has been clouded by media-amplified fears generated
by organisations and individuals opposed to any use of modern biotechnology,
and confusion caused by trade-motivated use of selectively emphasised
evidence.
In USA the FDA has maintained its position that milk from bST-treated
cows is not significantly different from milk from untreated cows,
and as regards animal health points to its post-approval monitoring
program (PAMP). The PAMP was the most extensive post-approval study
ever conducted on any animal product in USA. Special drug experience
reports were submitted to FDA's Center for Veterinary Medicine (CVM)
every 90 days, including the status reports, units of product distributed,
etc, The herd component involved 28 commercial herds representing
1213 cows in key dairy States to reflect the health of dairy cattle
given POSILAC® (the trade name used by Monsanto for its bST
product) for a single lactation under commercial conditions. Stringent
requirements were placed on the participants regarding data collection,
record-keeping, veterinary consultation, daily observations, etc.
Information provided from the State tracking programme showed that
there had been no changes in the percentage of milk discarded due
to violative residues attributable to the use of POSILAC. Based
upon the results of the 28 herd study and summarisation of Adverse
Drug Experience Reports, CVM concluded that the effects of POSILAC
on animal safety and effectiveness were in close agreement with
the effects observed in pre-clearance studies. During public hearings
held on 29 May and 20 November 1996, FDA's Veterinary Medicine Advisory
Committee also concluded from the PAMP that the labelling for POSILAC
provides adequate pack directions for actual conditions of use and
that POSILAC is safe and has no adverse effect on the milk supply.
Published scientific studies in USA (e.g. White et al, 1994; Judge
et al, 1997) also supported the earlier conclusions.
In February 1999, FDA's Center for Veterinary Medicine (CVM) issued
an Update, in which it reported that it had conducted a review of
the human safety aspects of the use of rbST, stimulated by the product's
review for approval in Canada (see below). The CVM review upheld
the FDA's original conclusion that milk from cows treated with rbST
is safe for human consumption.
In 1998, FAO/WHO revisited bST in the light of the most up-to-date
research evidence. The Joint FAO/WHO Expert Committee on Food Additives
(JECFA), met at FAO in Rome from 17 to 26 February 1998. JECFA's
work on the safety of residues of veterinary drugs in food includes
establishing acceptable daily intakes (ADIs) and maximum residue
limits (MRLs) for certain drugs when they are administered to food-producing
animals in accordance with good animal husbandry practices. In the
area of maximum residue limits (MRL) for bST, JECFA found that available
data on the identity and concentration of residues in animal tissues
provide a wide margin of safety for consumption of residues in food
when the drug is used according to good practice in the use of veterinary
drugs. The Committee concluded that the presence of drug residues
in animal products does not present any human health concerns.
JECFA also considered possible problems such as the likelihood
of a possible increase in the udder disease mastitis in bST-treated
cows which could lead to contamination of milk with antibiotics
used to treat mastitis. It concluded that the use of bST will not
result in a higher risk to human health due to the use of antibiotics
to treat mastitis and that the increased potential for drug residues
in milk could be managed by practices currently in use by the dairy
industry and by following label directions for use.
The Codex Committee on Residues of Veterinary Drugs in Food (CCRDVF),
acting on the advice of JECFA, recommended that the Codex Alimentarius
Commission should adopt a Maximum Residue Limit (MRL) for bST in
food. The European Commission opposed the advancement of an MRL
for rbST to Step 8 of the procedure for Elaboration of a Codex Standard
which would mean a recommendation for acceptance by Codex. The EU
wished to retain the proposal at Step 7 until a full JECFA report
was available and the outcome of the Codex Committee on General
Principles. Nevertheless, the Chairman of the CCRDVF decided to
take the proposal forward for discussion in the Codex Commission
in June 1999, where, however, the matter was withdrawn from the
agenda.
Although the use of bST has been under review in Canada since 1990,
Canadian examination of the issues was brought to a head in 1998
following a company's application for approval. The Canadian Health
Department (Health Canada) referred the matter to two independent
committees set up at its request in 1998 "to review the adequacy
of scientific data and broader issues related to the use of bovine
growth hormone in Canada". The two committees were the Expert
Panel on Human Safety of rbST , set up by the Royal College of Physicians
and Surgeons of Canada, and the Expert Panel on rbST set up by the
Canadian Veterinary Medical Association (CVMA). The Expert Panel
on Human Safety "found no significant risk to human safety
through ingestion of products from rbST-injected animals".
However, the Panel of the CVMA found that rbST "presents a
sufficient and unacceptable threat to the safety of dairy cows"..
Health Canada concluded in January 1999 that "The findings
of the animal safety committee, when combined with our own assessment,
made it quite clear that Health Canada had to reject the request
for approval to use rbST in Canada, as it presents a sufficient
and unacceptable threat to the safety of dairy cows' (an animal
health finding directly contrary to FDA's).
In the European Union, the re-examination of the issues during
1999 has arisen from the fact that the moratorium since 1990 on
bST treatment (initially to give time to study the situation, and
extended in December 1994 mainly on animal welfare and socio-economic
grounds) is due to expire in December 1999.
The EU Scientific Committee on Veterinary Measures relating to
Public Health (SCVMPH) was asked to examine the use of bST to dairy
cows as a productivity aid to milk production. In particular the
Committee was invited to assess the possible direct and indirect
adverse effects on public health caused by the use of bST under
normal conditions. The Committee did not reach a clear-cut judgement,
but pointed to areas where it considered more research was needed,
concluding:
- "Direct risks associated with the use of rbST in dairy
cows appear to be related to the possible increase of IGF-1 levels
in milk. The diverse biological effects attributable to the intrinsic
activity of IGF-1, exerting a broad variety of metabolic responses
through endocrine, paracrine and autocrine mechanisms, make the
definition of an in vivo quantitative dose-effect relationship
virtually impossible.
- Risk characterisation has pointed to an association between
circulating IGF-1 levels and an increased relative risk of breast
and prostate cancer. In addition, the possible contribution of
life span exposure towards dietary IGF-1 and related proteins,
present in milk from rbST treated cows, to gut pathophysiology
particularly of infants, and to gut associated cancers need to
be evaluated.
- The available data basis for exposure assessment, i.e. the amount
of IGF-1 and/or its truncated forms excreted in milk following
the administration of rbST to dairy cows, is incomplete.
- In addition secondary risks associated with the use of rbST
in dairy cows are:
- Potential changes in milk protein composition which might
favour allergic reactions.
- An increased use of antimicrobial substances in the treatment
of rbST related mastitis which might lead to an increased
risk of residue formation in milk and to the selection of
resistant bacteria. "
In a parallel exercise, the EU Scientific Committee on Animal Health
and Animal Welfare (SCAHAW)was asked to report on the incidence
of mastitis and other disorders in dairy cows and on other aspects
of the welfare of dairy cows. The Committee stated
"bST use substantially increases foot problems, mastitis
and injection site reactions in dairy cows. These conditions are
painful and debilitating, leading to significantly poorer welfare
of the animals. bST also causes reproductive disorders. Therefore,
from the point of view of animal welfare and health, this substance
should not be used."
On the matter of animal health, the Canadian and EU assessments
run directly contrary to those of the FDA and JECFA. Opponents of
the use of bST argue that FDA is defending its past decision and
the interests of a US company, and that JECFA was unduly influenced
by the US position. Supporters of its use point out that FDA's assessment
was the only one based on actual experience and real data arising
from the PAMP.
The UK Veterinary Products Committee (VPC) has been asked by the
UK Government to review the latest scientific information relating
to the safety of bST. A VPC Working Group of experts in veterinary
medicine, toxicology and effects of IGF-1 has been set up.and is
expected to report to the VPC some time in Summer 1999, following
which the VPC report to Ministers will be published.
The science of the issues taken account of in the foregoing assessments
is considered in more detail below.
Human Health General
This may be considered in two categories, namely the possible effect
of bST itself and the possible effect of IGF-1.
The above-mentioned clinical studies on treatment of human dwarfism
established that bST does not elicit any of its recognisable biological
actions in humans even if injected. The reason for this is that,
in consequence of its amino acid sequence, its three-dimensional
shape differs by about 35% from that of HST. To have a biological
effect, a protein hormone must first bind to a specific receptor
on the cell surface. The amino acid sequence dependent shape determines
whether the protein will be able to bind to a receptor. Receptor
binding studies have shown that the affinity for bST of human receptors
is very much less (10,000 to 100,000 times) than their affinity
for human somatotropin and thus bST has negligible hormone activity
in humans. (Moore et al, 1985; Hoquette et al, 1989; Souza et al.
1995).
The trace level of bST in milk does not differ significantly regardless
of whether or not the animal has received supplemental bST. Furthermore,
heat treatment, such as occurs with pasteurisation, inactivates
90% of the bST in milk. bST which is present in consumed milk is
not absorbed as such. It is digested like any other protein to single
amino acids and oligopeptides by protease enzymes in the stomach
and small intestines. Protein hormones such as bST have to be injected
directly into the body to be biologically active (e.g. insulin injections
taken by a diabetic). However, only HST is active in humans and
bST has no biological effects even if injected directly into the
body.
It may therefore be concluded that bST itself in milk is not a
matter of human health concern.
However, bST, whether natural or injected into cows, causes increased
milk production by promoting production of the hormone IGF-1, and
IGF-1 is present in the milk.
Three questions then arise, namely
- Is there an increased IGF-1 level in the milk of cows supplemented with bST?
- If there is an increased level, to what extent does it reflect
itself in an increased level in the human body?
- To what extent would any increase in IGF-1 in the human body
be a health concern?
On the matter of comparative IGF-1 levels, various studies have
reported inconsistent values, partly due to variations in analytical
methods and partly due to the fact that natural IGF-1 content of
milk varies widely depending on the stage of lactation, the age
of the cow, and management of the herd. During a lactation period,
a typical IGF-1 profile in cow's milk varies from 150 ng/ml after
parturition to 25 ng/ml at the end of the first week of lactation,
to 1 to 5 ng/ml at day 200 of lactation (Prosser, 1988; Xu, 1998).
In colostrum of cows which had not been treated with somatotropins,
IGF-1 exists in a truncated form. In this form three amino-acids
(glycine, proline and glutamate), have been deleted from the N-terminal
end. This truncated IGF-1, known as destripeptide IGF-1, has been
estimated to be between 5 and 10 times more potent than IGF-1 (Shimanoto,
1992).
IGF-1 concentrations in milk are much higher in the early phase
of lactation, a period before bST supplements are used. Colostrum
milk (produced at the onset of lactation) has especially high concentrations
of IGF-1 (up to 500 times greater than normal milk). The first few
days of lactation is also a period in which the newborn of many
species can absorb whole proteins. However, in this situation the
oral administration of IGF-1, even in pharmacological doses, does
not affect circulating concentrations of IGF-1 in the neonate (Donovan
and Odle, 1994; Odle et al., 1996; Burrin, 1997; Burrin et al, 1997).
Direct measurements using radiolabelled IGF-1 demonstrate that intestinal
absorption of IGF-1 is negligible (Donovan et al, 1997).
A comparison of retail milk originating from 'labelled' milk (from
non-treated cows) and 'non-labelled' milk (non-specified samples
originating from treated and non-treated cows) demonstrated an insignificant
increase of IGF-1 concentrations in the non-labelled milk samples
(Eppard et al, 1994). However, in this study the actual number of
animals treated with commercial rbST is not known.
Prosser et al (1989) showed a 3.6-fold increase in the IGF-1 concentration
over a 7-day period of treatment. In 1994, Burton et al highlighted
several studies demonstrating a two to fivefold increase of IGF-1
as a consequence of rbST treatment (Van den Berg, 1989; Gluckman,
1990; Groenewegen et al, 1990; Juskevich and Guyer, 1990).
Zhao et al (1994) reported on experimental daily injection and
administration of a sustained release formulation of bST to 74 lactating
cows. Treatments began in the fourth week of lactation and lasted
40 weeks. IGF-1 was monitored through early, mid- and late lactation.
bST treatment resulted in a significant increase of plasma IGF-1
in all lactation periods for both treatment groups. A higher milk
IGF-1 concentration, however, only occurred in mid- and late lactation
periods for the daily injection (application of bST is normally
restricted to the mid- and late lactation).
The JECFA Report (1998) cites average control values for IGF-1
in milk of 3.7 ng/ml for untreated cows, and a significant increase
to an average of 5.9 ng/ml as a consequence of bST-treatment (FAO
FNP 41/5, 1993). Similarly, studies by different pharmaceutical
companies report an increase of IGF-1 levels in milk between 25
and 70 percent in individual animals (Burton et al, 1994).
Bovine IGF-1 and human IGF-1 are identical in structure. IGF-1
is a normal component in human gastrointestinal secretions; and
concentrations in these secretions (e.g. saliva) are higher than
in milk. In fact, the amount of IGF-1 contained in 1.5 litres of
milk is less than 1% of the IGF-1 present in human daily gastrointestinal
secretions (FAO/WHO, 1998). Moreover, IGF-1 is a normal component
of blood and other body fluids; and the concentration in the blood
of adults and children can be over 100 times greater than found
in cows' milk. The amount of IGF-1 in 1.5 litres of milk is less
than 0.1% of the amount our body produces each day (Bauman, 1995;
FAO/WHO, 1998). Thus, the amount of IGF-1 in milk is extremely small
compared with our bodies' daily production. it may be argued that
any increase in IGF-1 as a result of bST treatment is negligible
compared with either the amount of IGF-1 produced in our own daily
gastrointestinal secretions or our own total production of IGF-1.
IGF-1 is broken down in the human digestive system in the same way
as other proteins including bST. Milk is but one of the many protein
sources we consume in the diet and the IGF-1 in milk comprises one-tenth
of one millionth of the total milk proteins (Bauman, 1995).
However, it is not only a question of how much additional IGF-1
is in the milk, but what happens to it. Unlike bST, IGF-1 is not
destroyed by normal milk pasteurisation conditions. Bovine IGF-1
is not denatured by normal pasteurisation (79° C for 45 seconds)
but following processing of milk for infant formula (121° C for
5 minutes) IGF-1 is no longer detectable (Collier et al., 1991).
In contrast an increase of measurable IGF-1 levels up to 70% following
pasteurisation has been reported (Juskevich and Guyer, 1990) the
different analytical methods applied allow no direct comparison
of these different reports.
Having regard to all the foregoing factors, consumption of milk
from bST-treated cows can result in only a negligible increase of
IGF-1 to be absorbed by the body or enter the blood.
Despite this, there has been concern and speculation about what
might be the effect of a lifetime's exposure to even a very small
increase in IG-1 in the body, and research has particularly centred
on the possibility of cancer promotion.
Human Health - IGF-1 and Cancer?
Concern and media stories have been fuelled by statements from
Dr Samuel Epstein of the University of Chicago (for many years an
activist opponent of 'chemicals in food'). In 1994, when the US
Food and Drug Administration (FDA) was in the process of approving
the use of bST, he made allegations that milk from cows supplemented with bST was a potential risk factor in breast and gastrointestinal
cancers. This was strongly refuted by FDA in a statement of 16 March
1994:-
"FDA has been receiving inquiries about whether insulin-like
growth factor (IGF-1) associated with the use of recombinant bovine
somatotropin (rbST) in dairy cows could have adverse effects on
people who consume the milk from treated cows. Specifically, allegations
have been made that dietary IGF-1 will cause breast cancer .......
FDA and other scientific and regulatory bodies have thoroughly
examined the safety of milk produced by rbST-treated cows and
have concluded that it is safe. The consumption of dietary IGF-1
plays no role in either inducing or promoting any human disease,
nor does it cause malignant transformations of normal human breast
cells .........the suggestion that IGF-1 in milk can induce or
promote breast cancer in humans is scientifically unfounded and
misguided. FDA has determined that milk from rbST-treated cows
is safe for human consumption and has not been found to be different
from milk from non-treated cows."
In January 1996, in an article in the International Journal of
Health Services (which is not a research journal) Dr Epstein, who
is on its editorial board, resurrected his allegations, and repeated
them in a series of media interviews. Dr Epstein's renewed allegations
were rejected by the American Cancer Society which stated "there
are no valid scientific findings to indicate a risk of carcinogenesis".
In 1998 Dr Epstein raised the cancer issue again in the same journal,
this time in relation to prostate cancer.
A prospective study was published by Hankinson et al (1998) in
which the IGF-1 content of blood samples taken in 1989-90 from women
within the Nurses Health Study cohort in USA were correlated with
subsequent occurrence of breast cancer, and in which there was a
positive relationship with circulating IGF-1 concentration among
premenstrual but not postmenstrual women nor in the whole study
population. It is notable that the study refers to a large amount
of data collected about the subjects, but not their dietary information
or habits. It is also notable that the blood samples were taken
some 4-5 years before the start of treatment of cows with bST. The
findings, which appear to run contrary to the concept of "a
lifetimes exposure", merit further investigation.
Consideration by the EU SCVPH is best conveyed by the relevant
extract from its March 1999 Report (see Appendix 1).
Antibiotic Residues in Milk
Discussion about mastitis (see Animal Health, below) has fuelled
concerns of increased use of antibiotics and of increase in their
residues in milk. The level of antibiotic residues in milk has been
strictly controlled in the UK for many years. Such controls are
also laid down in EC Directives on Milk (85/397/EEC and 92/46/EEC)
and the EC Regulation on Maximum Residue Limits (EEC/2377/90). Both
in the UK and USA, there are very tough financial penalties on producers
exceeding the tight limits laid down. During May to November 1994,
in New York State, 83 antibiotic violations were detected, seven
fewer than occurred in the same (pre-bST) period in 1993.
The risk of allergy due to antibiotics in milk has been assessed,
and Dewdney et al (1991) have concluded that the currently established
permitted levels of penicillin in milk and meat products are appropriate
to safeguard human health. The allergenicities of both bST and IGF-1
(whether in milk from treated or untreated cows) are low and are
comparable with those of other proteinaceous components of milk.
Mastitis and Somatic Cell Count
The EU Committee on Veterinary Medicinal Products (CVMP) considered
that a sufficient number of animals had been treated in clinical
trials to test the effect of somatotropin on the incidence of mastitis.
They concluded that, using conventional statistical techniques,
there was no evidence of a significant direct treatment-related
effect on mastitis. The incidence of mastitis is linked to milk
yield. bST treated cows have a higher incidence of mastitis and
more somatic cells in milk than lower yielding controls, but the
levels are comparable with untreated cows with a similar yield.
Other means of increasing milk yield, such as selective breeding,
have also been seen to increase the incidence of mastitis. There
is evidence that bST may reduce the severity of mastitis in treated
animals (Burvenich et al, 1988). In such circumstances, animals
treated with bST would suffer less pain and for a shorter duration
than untreated animals of similar yield.
In fact, after over a year of use of bST in USA, during which,
in the major dairy state of New York alone, bST treatment had been
given to 335,000 cows (45% of the state total) the New York State
Mastitis Control Program reported "There is no indication that
bST has had any effect in increasing mastitis.".
Susceptibility to mastitis is related to many factors, especially
environmental conditions and milking management practices. At the
bST/Mastitis public hearing, FDA and the Expert Advisory Committee
considered results from bST studies and concluded affects were of
no biological significance because they were inconsequential relative
to the major causes of mastitis. In the first instance, typically
30 to 50% of mastitis cases occur in the first 60 days postpartum
- a period when bST is not even used. Secondly, they pointed out
that the impact of bST was minor as a cause of mastitis - for example,
the effect of season was 9.8-fold greater, the effect of parity
was 6.5-fold greater, the effect of herd was 4.8-fold greater, and
the effect of stage of lactation was 7.1-fold greater, to name just
a few factors.
Furthermore, bST does not alter typical relationships between herd
factors and incidence of clinical mastitis. Once all the major factors
causing mastitis were accounted for, there remained a small positive
relationship between milk yield and the incidence of mastitis when
expressed on a per cow basis, and bST treatment did not alter this
relationship. However, from both a consumer and farmer perspective
a more realistic evaluation of risk is to consider cases of mastitis
per volume of milk produced. When expressed per unit of milk, mastitis
incidence declined slightly as milk yield increased and this relationship
was not altered by bST (e.g. White et al, 1994). Therefore, the
higher producing bST-treated cow presents a lower risk per unit
of milk than the same cow not administered bST.
The higher somatic cell count in milk from high-yielding cows and
bST treated cows is not a problem. Somatic cell count in milk is
monitored, and milk for human consumption must have a mean somatic
cell count below 400,000 per ml, in accordance with EU Directive
92/46/EEC.
Antibiotic Residues in Milk
Discussion about mastitis has fuelled concerns of increased use
of antibiotics and of increase in their residues in milk. The level
of antibiotic residues in milk has been strictly controlled in the
UK for many years. Such controls are also laid down in EC Directives
on Milk (85/397/EEC and 92/46/EEC) and the EC Regulation on Maximum
Residue Limits (EEC/2377/90). Both in the UK and USA, there are
very tough financial penalties on producers exceeding the tight
limits laid down. During May to November 1994, in New York State,
83 antibiotic violations were detected, seven fewer than occurred
in the same (pre-bST) period in 1993.
In 1998, FAO/WHO revisited bST in the light of the most up-to-date
research evidence. The Joint FAO/WHO Expert Committee on Food Additives
(JECFA), met at FAO in Rome from 17 to 26 February 1998 to evaluate
certain residues of veterinary drugs in food. JECFA considered possible
problems such as the likelihood of a possible increase in the udder
disease mastitis in bST-treated cows which could lead to contamination
of milk with antibiotics used to treat mastitis. The Committee concluded
that the use of bST will not result in a higher risk to human health
due to the use of antibiotics to treat mastitis and that the increased
potential for drug residues in milk could be managed by practices
currently in use by the dairy industry and by following label directions
for use. JECFA's further concusions are referred to below
The risk of allergy due to antibiotics in milk has been assessed,
and Dewdney et al (1991) have concluded that the currently established
permitted levels of penicillin in milk and meat products are appropriate
to safeguard human health. The allergenicities of both bST and IGF-1
(whether in milk from treated or untreated cows) are low and are
comparable with those of other proteinaceous components of milk.
Animal Health and Welfare - General
Within the whole subject of bST treatment of cows, its effect on
animal health and welfare, and in particular on the incidence of
mastitis, has been, and remains, the area of greatest controversy.
The Institute's nine-point policy statement on "the public
interest in respect of food" includes
"Animal Welfare - that where animals are used in food production,
responsible attention should be paid to their welfare".
In its 1999 Report, the EU Scientific Committee on Animal Health
and Animal Welfare (SCAHAW) expressed the emphatic view that bST
use substantially increases foot disorders, mastitis, reproductive
disorders and other production related diseases, problems which,
it stated, would not occur if bST were not used and which often
result in unnecessary pain, suffering and distress. It added that
if milk yields were achieved by other means which resulted in these
health disorders and other welfare problems, those means would not
by acceptable. The injection of bST and its repetition every 14
days was said also to cause localised swellings, likely to result
in discomfort and hence poor welfare.
However, at least with regard to mastitis, this view is contradicted
by earlier EU findings based on clinical trials, experience in USA,
and the results of some researchers.
Animal Health - Mastitis
The incidence of mastitis is linked to milk yield. bST-treated
cows have a higher incidence of mastitis and more somatic cells
in milk than lower yielding controls, but the levels are comparable
with untreated cows with a similar yield. Other means of increasing
milk yield, such as selective breeding, have also been seen to increase
the incidence of mastitis.
In 1993 the EU Committee on Veterinary Medicinal Products (CVMP)
considered that a sufficient number of animals had been treated
in clinical trials to test the effect of bST on the incidence of
mastitis. They concluded that, using conventional statistical techniques,
there was no evidence of a significant direct treatment-related
effect on mastitis.
There is evidence that bST may reduce the severity of mastitis
in treated animals (Burvenich et al, 1988). In such circumstances,
animals treated with bST would suffer less pain and for a shorter
duration than untreated animals of similar yield.
After over a year of use of bST in USA, during which, in the major
dairy State of New York alone, bST treatment had been given to 335,000
cows (45% of the state total) the New York State Mastitis Control
Program reported "There is no indication that bST has had any
effect in increasing mastitis.".
Susceptibility to mastitis is related to many factors, especially
environmental conditions and milking management practices. At the
bST/Mastitis public hearing, FDA and the Expert Advisory Committee
considered results from bST studies and concluded that effects were
of no biological significance because they were inconsequential
relative to the major causes of mastitis. In the first instance,
typically 30 to 50% of mastitis cases occur in the first 60 days
postpartum - a period when bST is not even used. Secondly, they
pointed out that the impact of bST was minor as a cause of mastitis
- for example, the effect of season was 9.8-fold greater; the effect
of parity was 6.5-fold greater; the effect of herd was 4.8-fold
greater; and the effect of stage of lactation was 7.1-fold greater.
Furthermore, bST does not alter typical relationships between herd
factors and incidence of clinical mastitis. Once all the major factors
causing mastitis were accounted for, there remained a small positive
relationship between milk yield and the incidence of mastitis when
expressed on a per cow basis, and bST treatment did not alter this
relationship. However, from both a consumer and farmer perspective
a more realistic evaluation of risk is to consider cases of mastitis
per volume of milk produced. When expressed per unit of milk, mastitis
incidence declined slightly as milk yield increased and this relationship
was not altered by bST (e.g. White et al, 1994). Therefore, it was
argued, the higher producing bST-treated cow presents a lower risk
per unit of milk than the same cow not administered bST.
It has been claimed that US results illustrate that bST-supplemented
cows are healthier because farmers have routinely gone to extended
lactations. This change is possible because bST increases the persistency
of lactation (Van Amburgh et al, 1997). That paper concluded
"On a herd base, through two years of studies (with bST),
extended calving interval resulted in fewer calvings, lower incidence
of postpartum metabolic diseases, lower veterinary costs, less
culling with fewer replacements needed, and an overall improvement
in herd life, animal well-being and dairy profitability."
Socio-economic Concerns
Before the introduction of bST treatment in USA in February 1994,
there was much debate about such issues as the effect of permitting
bST treatment on the overall volume of milk produced, on the economics
of production and pricing, and on the effects on large and small
producers. Discussion at length of socio-economic hypotheses is
outside the scope of this paper. However it is worth observing that
this is a technology involving no capital cost and therefore readily
utilised equally by large and small farmers; and that, in a situation
where supply outstrips demand, or is restricted (as in the EU) by
quotas, farmers would be likely to use the technology to improve
productivity rather than production volume, i.e. the same volume
of milk production from fewer cows.
In the event, in the ensuing five years of practical experience
none of the forecast adverse effects has come to pass. The conditions
of use of bST in the USA are similar to those that would apply in
the UK and Europe (described above), one of the major differences
being that sales are not subject to the need for a veterinary prescription.
The arrangements for the product's distribution ensure that veterinary
expertise and advice is provided to farmers before the product is
used.
Monsanto's bST product is licensed in the USA for administration
to healthy dairy cows. It went on sale on 4 February 1994 under
the trade name 'POSILAC'. At January 1998, of nearly 9 million dairy
cows in USA, around 25% are in treated herds, and 300 additional
dairy farmers a month are reported to be taking up its use . The
average dairy farmer using POSILAC is supplementing more than 50%
of the herd at any one time, dependent on individual herd management
practices and stage of the adoption.
Overall usage showed an increase of 45% in 1996 over 1995; and
a further increase of 30 per cent in 1997 over 1996.
Despite hostile media coverage, the activities of anti-bST pressure
groups and the initial reaction of several US supermarket chains
to the effect that they would not purchase bST derived milk and
milk products, milk consumption, far from falling, slightly increased.
US Department of Agriculture data showed that In the first 10 months
of 1994, liquid milk consumption increased by 1% over (pre-bST)
1993; milk prices received by farmers did not plummet but increased
slightly; farmers using bST did increase their productivity; and,
far from large farmers using the technique exclusively and driving
small farmers out of business, the size of herds supplemented with
bST closely resembled the distribution of herd sizes found in USA,
and 55% of all sales of bST have been to farmers with 100 or fewer
cows (Hartnell, 1995).
Labeling Problems
In the early days of the use of bST treatment in the USA, some
suppliers of milk from sources where bST treatment had not been
used, and of milk products made from such milk, sought to label
them "bST free". FDA would not permit this, on the grounds
that no milk is bST free. However, US regulations do allow niche
market labelling of food products as long as the label is truthful
and accurate. Thus, FDA allows a label stating that bST treatment
has not been used provided that the farmer signs an affidavit that
he has not used the bST treatment in his herd. Currently in the
USA a small percentage of the fluid milk sales represent milk labelled
as coming from cows not treated with bST; for example in upstate
New York this is less than 1% of total fluid sales. This is not
easy to apply in distribution systems where milk from farms in a
geographical are is bulked regardless, though in these days where
segregation and traceability of raw materials have assumed a greater
importance, that difficulty may be more easily overcome. It is easy
to apply where the supply goes direct to the consumer or to the
milk products manufacturer from a single farm or a group of farms
none of which is using BSE treatment.
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Editorial Footnotes
Before issue, IFST draft Position Statements go through a vetting
procedure by the Technical & Legislative Committee and the Public
Affairs Committee, to ensure that the contents are scientifically
valid, entirely objective and suitable to be issued in the name
of the Institute. As this work is being done by volunteer members
as a spare-time activity, there are obvious limitations on the frequency
with which such procedure can be invoked.
As an interim means of providing additional up-to-date information
to visitors to our Web site, the device of "Editorial Footnotes"
is adopted. These are written by the IFST Web Editor, in consultation
with other members of the relevant Position Statement drafting team,
and are provisional..
Editorial Footnotes
Editorial Footnote [1] dated 25 January 2000. Report of UK Veterinary
Products Committee
Editorial Footnote [2] dated 25 January 2000. Continued European
Moratorium on Use of bST
The Institute of Food Science & Technology (IFST) is
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