The safety of food for human consumption is based on the concept that there should be areasonable certainty that no harm will result fromintended uses under the anticipated conditions of consumption
The consideration of the safety of foods and food components derived from biotechnology
involves several continua: from older to newer biotechnology; from traditional techniques to the
latest techniques based on molecular and cellular biology; from simple to complex products; from a
well-known history of exposure and safety of use to areas of less knowledge of the trait in different
organisms; from whole organisms to specific chemical compounds or substances; and from simple to
complex assessment approaches. For a rational and practical approach to ensuring safe use, these
continua can be separated into manageable pieces, facilitating the description of the concepts or
principles of safety. Accordingly, scientific principles and procedures should be applied in a flexible
fashion, taking into account the knowledge of: the characteristics of the newly introduced trait(s);
potential dietary exposure; the preparation and processing of the foods or food components;
nutritional considerations; and toxicological aspects.
Concepts of food safety
The safety of food for human consumption is based on the concept that there should be a
reasonable certainty that no harm will result from intended uses under the anticipated conditions of
consumption. Historically, foods prepared and used in traditional ways have been considered to be
safe on the basis of long-term experience, even though they may have contained natural toxicants or
anti-nutritional substances. In principle, food has been presumed to be safe unless a significant hazard
was identified.
Modern biotechnology broadens the scope of the genetic changes that can be made in food
organisms, and broadens the scope of possible sources of foods. This does not inherently lead to
foods that are less safe than those developed by conventional techniques. Therefore, evaluation of
foods and food components obtained from organisms developed by the application of the newer
techniques does not necessitate a fundamental change in established principles, nor does it require a
different standard of safety.
Moreover, the precision inherent in the use of certain molecular techniques for developing
organisms for use as food should enable direct and focused assessment of safety where such
assessment is desired. Knowledge obtained using these methods might also be used to approach
safety assessment of new foods or food components from organisms developed by traditional
methods.11
Safety considerations and substantial equivalence
For foods and food components from organisms developed by the application of modern
biotechnology, the most practical approach to the determination of safety is to consider whether they
are substantially equivalent to analogous conventional food product(s), if such exist. Account should
be taken of the processing that the food may undergo, as well as the intended use and the exposure.
Exposure includes such parameters as the amount of food or food component(s) in the diet, the pattern
of dietary consumption, and the characteristics of the consuming population(s). This approach
provides a basis for an evaluation of food safety and nutritional quality.
The concept of substantial equivalence embodies the idea that existing organisms used as food,
or as a source of food, can be used as the basis for comparison when assessing the safety of human
consumption of a food or food component that has been modified or is new.
If one considers a modified traditional food about which there is extensive knowledge on the
range of possible toxicants, critical nutrients or other relevant characteristics, the new product can be
compared with the old in simple ways. These ways can include, inter alia, appropriate traditionally
performed analytical measurements (for example, alkaloid levels in potatoes, cucurbatin in vegetable
squash cultivars, and psoralens in celery) or crop-specific markers, for comparative purposes. The
situation becomes more complex as the origins/composition/exposure experience decreases, or if the
new products lack similarity to old established products or, in fact, have no conventional counterpart.
A demonstration of substantial equivalence takes into consideration a number of factors, such as:
− knowledge of the composition and characteristics of the traditional or parental product or
organism;
− knowledge of the characteristics of the new component(s) or trait(s) derived, as appropriate,
from information concerning: the component(s) or trait(s) as expressed in the precursor(s)
or parental organism(s); transformation techniques (as related to understanding the
characteristics of the product) including the vector(s) and any marker genes used; possible
secondary effects of the modification; and the characterisation of the components or trait(s)
as expressed in the new organism; and
− knowledge of the new product/organism with the new components or trait(s), including the
characteristics and composition [i.e. the amount of the components or the range(s) of
expression(s) of the new trait(s)] as compare with the conventional counterpart(s) (i.e. the
existing food or food component).
Based on a consideration of the factors in the paragraph above, knowledge that a new food or
food component(s) was derived from organism(s) whose newly introduced traits have been
well-characterised, together with a conclusion that there is reasonable certainty of no harm as
compared with its conventional or traditional counterpart, means that a new food or food
component(s) can be considered substantially equivalent.
Set out below are the principles for the application of substantial equivalence to the assessment
of foods from organisms developed by the application of biotechnology:
− If the new or modified food or food component is determined to be substantially equivalent
to an existing food, then further safety or nutritional concerns are expected to be
insignificant;12
− Such foods, once substantial equivalence has been established, are treated in the same
manner as their analogous conventional counterparts;
− Where new foods or classes of new foods or food components are less well-known, the
concept of substantial equivalence is more difficult to apply; such new foods or food
components are evaluated taking into account the experience gained in the evaluations of
similar materials (for example, whole foods or food components such as proteins, fats or
carbohydrates);
− Where a product is determined not to be substantially equivalent, the identified differences
should be the focus of further evaluations;
− Where there is no basis for comparison of a new food or food component, that is, where no
counterpart or similar materials have been previously consumed as food, then the new food
or food component should be evaluated on the basis of its own composition and properties.
As an example of the application of substantial equivalence, potatoes have long been part of the
human diet. The presence of viral coat proteins in the potato are due to natural viral infections;
consequently, these proteins have a long history of human consumption. Coat proteins have never
been associated with a toxicity problem and are not considered a food safety issue. Consequently, a
potato in which the coat protein of one of these viruses is expressed after the gene has been introduced
would be considered substantially equivalent to the infected potatoes that have a long history of safe
use and consumption provided the amounts expressed were not grossly different from those occurring
following natural infection. This analogy applies only to viral coat proteins in the portions of the
plant traditionally consumed, taking into account the characteristics of the new trait and possible
untoward effects of the modification on alkaloid levels and key nutrient starches, as well as the extent
of consumption.
Some specific examples of additional considerations which it may be necessary to take into
account when applying the concept of substantial equivalence are indicated in the following
paragraphs.
The intended use(s) and degree of exposure must also be considered in assessing safety. This
includes the effect(s) of the level of the food or food component in the diet, the pattern of dietary
consumption, and the characteristics of the consuming populations (i.e. infants, the elderly, the
immunocompromised, etc.).
The consideration of safety may include the need to evaluate possible effects occurring through
cooking or other processing. For example, trypsin inhibitors from certain leguminous plants, such as
the cowpea trypsin inhibitor, have a long history of safe consumption when properly cooked.
However, if the cowpea trypsin inhibitor is expressed in other plants, the safety question relates to
whether the normal use of these plants as food involves cooking sufficient for its inactivation.
In special cases, depending on the product consumed, the consideration of safety may also
include the need to evaluate the potential for, and human health implications of, transfer of the new
genetic material. For example, the use of some antibiotic resistance markers in micro-organisms
should be carefully considered since transfer to the microflora of the human gut could, if
demonstrated, possibly have human health implications.
Another consideration is the influence of the newly introduced modifications on the nutritional
value of the food or food component(s). For the majority of modifications being carried out, such13
changes are unlikely. Nonetheless, when modifications are directed at metabolic pathways of key
macro or micro nutrients, the possibility of an impact on nutritional value is increased. Such impacts
are of potential significance in cases where the modified food or food component may become a major
dietary source of the nutrient affected.
Conclusions
The main conclusion of this report is as follows: if a new food or food component is found to be
substantially equivalent to an existing food or food component, it can be treated in the same manner
with respect to safety. No additional safety concerns would be expected.
Where substantial equivalence is more difficult to establish because the food or food component
is either less well-known or totally new, then the identified differences, or the new characteristics,
should be the focus of further safety considerations.
Chapter III contains a number of case studies that illustrate the practical application of the
concepts and principles for safety evaluation of new foods or food components, in particular the
concept of substantial equivalence. In addition, the examples are representative of the range of new
products produced by means of biotechnology. Given the wide applicability of substantial
equivalence, experts on the Working Group were of the view that many new foods will be found to be
substantially equivalent to existing products.
In the case of those products for which substantial equivalence cannot be established, or for
which there is no traditional counterpart, further work will be helpful to increase our understanding of
the appropriate information which may be needed and the methods to be used for safety evaluation.
According to dbtbiosafety