Report of the Royal College of Physicians and Surgeons of
Canada Expert Panel on Human safety of rbST
Prepared for Health Canada, January 1999
Table of Contents
Executive Summary
At Health Canada's request, the Royal College of Physicians and
Surgeons of Canada established an expert panel in April of 1998
to examine the human safety issues pertinent to the use of rbST
in dairy cattle in Canada.
The panel was asked to "review international scientific reports
and conclusions that have been made about rbST"and "to make observations
and recommendations regarding the adequacy of the scientific data
submitted by the manufacturer of Nutrilac (rbST) or (to examine
scientific information) existing elsewhere to make sound scientific
assessments regarding the human health risks associated with the
use of Nutrilac (rbST) in Canadian dairy cattle."
The panel members were chosen for their expertise in medicine,
pediatrics, oncology, nutritional science, epidemiology, pharmacology
and toxicology. All are active or emeritus members of Canadian
Faculties of Medicine or Health Sciences. The panel operated
independently with a reporting relationship to the Royal College
of Physicians and Surgeons of Canada.
The panel reviewed an extraordinary volume of scientific data and
literature relevant to its task. The quality of the scientific
evidence available to the Bureau of Veterinary Drugs, Human Safety
Division with respect to the Nutrilac file appears to be excellent
and complete as far as is possible in a field of scientific study
which has evolved rapidly during the course of a review lasting
more than nine years. In particular, there is a quickly expanding
literature on biologic effects of insulin-like growth factor-1 (IGF-1),
which is indirectly relevant to the human safety of food products
from rbST-treated cattle. The panel experienced no difficulty
in finding up-to-date information required for its analysis.
It was apparent to the panel that scientific awareness of relevant
human safety issues within Health Canada has kept pace with growth
of scientific perception concerning somatotropin (ST) and IGF-1
during the 1990s.
The panel has reached a number of conclusions concerning the human
safety of food products from rbST-treated cattle.
- Cow's milk contains bST whether or not the cow has been treated
with rbST. No increase in total bST concentration is observed
in milk from rbST-treated cows and therefore no human risk related
to ST consumed by this route is likely to result.
- RbST given to rats in a 90-day study conducted by the manufacturer
caused an antibody response in some test animals, including one
that received a relatively low dose of 0.1 mg/kg/day. The
antibody response in question was detected at 14 weeks.
This effect, if validated, would suggest the possibility of occasional
hypersensitivity reactions in those consuming food products from
rbST-treated cattle. The panel recommends further discussion
of the antibody results by Health Canada scientists with the manufacturer
and repetition of the studies in question to clarify the risk
of hypersensitivity following exposure to oral rbST at low doses.
- RbST increases the production of IGF-1 concentrations in recipient
animals and IGF-1 concentrations are increased in
food products from rbST-treated cattle. The increments of
IGF-1 in milk and other food products represent a minor increase
in exposure for human recipients when compared to endogenous (physiological)
production of and exposure to IGF-1. The panel recognizes
major difficulties in drawing inferences about the potential for
indirect human toxicity related to the increased production of
IGF-1 in recipient animals. However, there is no biologically
plausible basis on which to conclude that rbST-associated changes
in human exposure to IGF-1 will lead to any immune response, change
in neonatal intestinal growth and development, or cancer risk
in recipients of milk or food products from treated cattle.
- Apart from concern, as noted above, about the antibody response
observed in a single rat treated subchronically (90 days) with
rbST at a dose of 0.1 mg/kg/day, the panel does not think that
chronic toxicity or reproductive studies in laboratory animals
are justified since there are no receptor-mediated rbST effects
in human.
- Biological study of IGF-1 will remain of exceptional interest;
however, there is no evidence to suggest that oral intake of IGF-1
is carcinogenic. As an endogenous substance, IGF-1 may play
a role in the pathophysiology of neoplasia; however, Health Canada
would not be justified in requiring further studies of IGF-1 to
be conducted by the manufacturer of Nutrilac with respect to the
pathogenesis of human malignancy.
- It appears that the incidence of mastitis increases in rbST-treated
cows and that this condition is likely to be treated on many Canadian
farms with antibiotics. The panel does not consider that
these events pose a risk to human safety since Canada has an enforced
testing program for all milk pooled in tank reservoirs.
That program will assure that antibiotic residues are maintained
within nationally accepted standards. Furthermore, the panel
thinks that any increase in exposure of bacteria to antibiotics
as a result of rbST-related mastitis would be of marginal importance
compared to the effects of antibiotic exposure resulting from
other agricultural and human antibiotic uses. It is highly
unlikely that rbST use will have any impact on the important public
health issue of increasing antibiotic resistance.
In summary, with one exception, the panel finds no biologically
plausible reason for concern about human safety if rbST were to
be approved for sale in Canada. The only exception to this
statement is the occurrence of an antibody reaction (possible hypersensitivity)
in a subchronic (90-day) study of rbST oral toxicity in rats that
resulted in one test animal developing an antibody response at low
dose (0.1 mg/kg/day) after 14 weeks. In the opinion of the
panel, this anomalous result deserves further study, including discussion
between the manufacturer of Nutrilac and Health Canada scientists.
The panel recommends, on the basis of present knowledge, that the
study in question be repeated.
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Table of Contents
The report has been prepared as one HTML file (82K) for easier
printing.
- Report of the rbST Human Safety Panel
- Background
- Conflict of interest screening
- Panel membership
- Operation of panel
- Questions posed to the panel
- The challenge of indirect risk assessment in human toxicology
- Comments re: review process
- Review of international scientific reports and literature
- Discussion of Human Safety Issues
Related to rbST
- Human exposure to bovine food products
- Pharmacology/toxicology of somatotropin
- IGF-1
- Somatotropin effects on the composition and characteristics
of bovine products
- Controversies
- Conclusions
- References
- Glossary
- Appendix 1: Information
distributed to human safety panel members
- Appendix 2: Monsanto 90-day
study: determination of sometribove
immunoglobulin in rat serum
Media Inquiries
Margot Geduld
(613) 957-1588
Committee membership
- Dr. Stuart M. MacLeod (Chair)
Professor, Departments of Clinical Epidemiology and Biostatistics,
Medicine and Pediatrics,
McMaster University, Hamilton, Ontario
- Dr. Réjeanne Gougeon
Assistant Professor, Nutrition and Food Science Centre,
Faculty of Medicine, McGill University,
with cross-appointment in the School of Dietetics and Human Nutrition,
Faculty of Agricultural and Environmental Sciences,
McGill University, Montreal, Quebec
- Dr. Gerald S. Marks
Professor Emeritus, Department of Pharmacology and Toxicology,
Queen's University, Kingston, Ontario
- Dr. Michael Pollak
Professor, Departments of Medicine and Oncology,
McGill University, Montreal, Quebec
- Dr. Milton Tenenbein
Professor,
Departments of Pediatrics and Pharmacology and Therapeutics,
University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba
- Ms. Cindy Woodland (Research Assistant to the Committee)
Doctoral Candidate, Department of Pharmacology,
Division of Clinical Pharmacology and Toxicology,
The Hospital for Sick Children,
University of Toronto, Toronto, Ontario
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