Feed additives, including feed flavorings, require a thorough
evaluation of consumer safety (Fig. 1). As presented by the European
Food Safety Authority (EFSA, 2012a), such an evaluation can
be seen as a four step process from hazard characterization in
laboratory animals or available literature through to determination
of additive residues in the consumable target species. Step 1 is a
hazard characterization usually done in rats, which will also
include the kinetic and metabolic profiling of the additive. Step 2 is
the comparison of these rat data with the kinetics and metabolism
of the feed additive in the target livestock species to determine the
identity and amount of the major metabolites. In case the target
animal would form species-specific metabolites that were not
present in the laboratory rat, gathering additional toxicological
information about this metabolite would be warranted. Step 3
consists of determination of relevant residue levels in the edible
animals for experimental purposes, we find it timely to present our
case study of a modified approach to the safety assessment of feed
additives thereby using and combining alternative methods. While
the overall focus must remain on safety to the consumer, by
providing alternative approaches for each step in the hazard characterization
process, the current evaluation demonstrated that it is
possible to reduce or avoid animal studies.
Information for hazard characterization can be obtained from
literature from entries in databases such as that available from the
European Chemicals Agency (ECHA). However, it may be that the
tissues of livestock. In Step 4, the risk characterization for the feed
additive is derived based on the exposure of the consumer to the
substance and its metabolites' via edible tissues that is then
compared to the Health Based Guidance Values such as the
Acceptable Daily Intake (ADI) derived from toxicological studies.
Briefly, step 1 requires gathering the relevant toxicological
(hazard) information either from literature (original literature and/
or reviews from competent bodies such as EFSA or the Joint FAO/
WHO Expert Committee on Food Additives (JECFA)) or from specifically
designed toxicological studies, step 2 requires metabolism
studies in laboratory rat and target species using radiolabelled
material. Step 3 requires the feeding of livestock animals followed
by collection of their edible tissues for analytical determination of
the residues' concentrations. Following the EFSA guidance document
(EFSA, 2012a) such an evaluation will require a rather
extensive use of both laboratory animals and livestock animals for
meeting the experimental objectives. Under normal farming conditions,
the target species animals would be marketed; however,
because of the nature of the experimental conditions, the remains
of the animals must be discarded.
With the current increased emphasis on reducing the use of