evaluation of certain food additives - libdoc.who.int - World Health ...

In the 2-year toxicity study, GR fed to Beagle dogs at dietary concentrations
of 0.05% or 1.0% had no effect on growth, feed consumption, survival, organ
weights, haematology, urinalysis, liver or kidney function, or gross or microscopic
histopathology. No significant dose-related systemic toxicity was
noted in dogs. The NOEL in this study was 1.0% in the diet (equivalent to
250 mg/kg bw per day).
The results of the studies with GR were compared with those of the related
substance wood rosin (WR). The Committee concluded that the results of
the studies with GR were consistent with those of the 90-day toxicity and 2-
year toxicity/carcinogenicity studies with WR in rats that were previously
evaluated (Annex 1, reference 116). Furthermore, the results from the 90-day
toxicity studies with GEWR indicate that the feed acceptance was improved.
This effect is reflected by the absence of deaths even in the highest GEWR
dose group (2500 mg/kg bw per day).
The Committee was informed by the sponsor of the results of two 90-day
toxicity studies with GEGR in rats for which the NOEL was claimed to be
1.0% in the diet. However, the full reports were not available for evaluation
by the Committee.
The variations in the amounts of both the individual resin acids and the components
of the neutral fraction were considered to be of no toxicological
consequence.
In its previous evaluation of GEWR at the forty-sixth meeting, the Committee
concluded that GEWR is metabolically stable in the gastrointestinal tract,
with more than 95% being recovered unchanged in the faeces. Only a minor
fraction, most probably the monoglycerol ester fraction, undergoes partial
hydrolysis (Annex 1, reference 116). Although the proportion of the monoglycerol
esters is dependent upon the ratio of the GR and the glycerol used
in the esterification process, the variations observed in the monoglycerol esters
of GEGR are comparable with those observed in the monoglycerol esters
of GEWR.
The Committee also considered the previous evaluation of the absorption
studies in rats with tritiated resin acids—namely, dehydroabietic, tetrahydroabietic
and isopimaric acids—which indicated that these resin acids were
primarily recovered from the faeces within 2 weeks (most within 4 days)
after oral administration. The small amount of dehydroabietic acid absorbed
appeared to have been metabolized in the liver to three or four
uncharacterized metabolites, which were then excreted in the bile and urine.
There was limited evidence to show that tetrahydroabietic and isopimaric
acids were metabolized.
In its previous evaluation of GEWR, the Committee concluded that GEWR
is not genotoxic in several in vitro test systems.
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