Agriculture Reference
In-Depth Information
the outcome of the repeated dose 90-day
oral toxicity study, further toxicological
testing may be needed (e.g. studies on
reproductive/developmental ef ects or on
chronic toxicity; see Chapters 5 and 8).
h e conclusion of the toxicological assess-
ment provides information on: (i) the
potential toxicity of the newly expressed
protein(s) and, if present, of other natural
constituents which might indicate adverse
ef ects on human and animal health; and (ii)
potential adverse ef ects of the whole food
and feed derived from the GM plant.
for allergenicity assessment of GMOs (CAC,
2009; EFSA, 2011a).
As indicated above, as Regulation (EC)
1829/2003 covers both GM food and feed,
and therefore the potential for allergenicity
in animals, both companion and livestock
animals must be taken into account. In this
context, the same principles apply to the
allergenicity assessment of food as well as
feed. h e allergenicity assessment of GM
plants and derived products, described in
the EFSA's 'Scientii c opinion on the assess-
ment of allergenicity of GM plants and
microorganisms and derived food and feed'
(EFSA, 2010c) and implemented in the EFSA
guidance (EFSA, 2011a), is divided into the
following.
Allergenicity is the potential of a substance
to cause an allergy. An allergy is a pathological
reaction of the immune response to that
particular substance. Food allergy is an
adverse immune response to food/feed and
is dif erent from toxic reactions and food
intolerance. h e majority of the substances
causing an allergic response to food and feed
are proteins.
Food allergy in humans, in food-
producing animals and in companion
animals has been described (EFSA, 2010c).
Immune-mediated adverse reactions have
been detected in pets (Verlinden
et al
., 2006)
as well as in food-producing animals, due to
the replacement of animal proteins with
vegetal proteins; for example, in young farm
animals such as calves and pigs (Dreau
and Lalles, 1999) and in intensively reared
i sh (Bakke-McKellep
et al
., 2007). However,
additional work is still needed for a
more comprehensive understanding of the
mechanisms involved in these immune-
mediated adverse reactions.
Food allergy can be caused by various
immune mechanisms and it is generally
divided into two forms, IgE mediated (e.g.
allergic reactions to peanuts or soybean) and
non-IgE mediated (e.g. allergic eosinophilic
gastroenteropathies). Since the form
provoking the most severe allergic reactions,
including anaphylaxis, is an IgE-mediated
food allergy, this has been the focus of
dif erent international guidance documents
Allergenicity assessment of newly expressed
proteins
h ere is not a single test that can predict the
allergenicity properties of a protein.
h erefore, both the EFSA (2010c, 2011a)
and Codex Alimentarius (CAC, 2009) recom-
mend a case-by-case, weight-of-evidence
approach to assess the allergenicity of newly
expressed protein(s). h e cumulative body
of evidence necessary for this assessment is
based on the comparison of amino acid
sequence similarity (bioinformatics search),
specii c serum screening, pepsin resistance
test, other
in vitro
digestibility tests and,
possibly, other studies (e.g.
in vitro
assays
and
in vivo
models).
h e EFSA (2010c, 2011a) also underlines
the importance of including an adjuvanticity
assessment of the newly expressed protein(s)
in the allergenicity assessment. Adjuvanticity
is the capacity of a substance to increase the
immune response to an antigen when
co-administered with that antigen. Strictly
speaking, and unlike allergens, adjuvants do
not have the capacity to trigger an allergic
reaction per se, since they lack sensitizing
potential. However, combined exposure to
an adjuvant and an antigen may boost the
immune response of an allergic individual/
animal to that particular antigen, causing
more severe adverse reactions than when
exposed to the antigen only.
