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

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 TOR were compared with those of the related
substance WR. The Committee concluded that the results of the studies with
TOR were consistent with those of both the 90-day toxicity and 2-year
toxicity/carcinogenicity studies with WR, which were previously evaluated
(Annex 1, reference 117). 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).
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% recovered unchanged in the faeces. Only a minor fraction,
most probably the monoglycerol ester fraction, undergoes partial hydrolysis
(Annex 1, reference 117). Although the proportion of the
monoglycerol esters is dependent upon the ratio of TOR to glycerol used in
the esterification process, the variations observed in the monoglycerol esters
of GETOR are comparable with those observed in the monoglycerol esters
of GEWR.
The Committee also considered the previous evaluation of the absorption
studies with tritiated resin acids in rats—namely, dehydroabietic, tetrahydroabietic
and isopimaric acids—which indicated that these resin acids were
primarily recovered in 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.
The Committee also noted the compositional differences that are unique to
TOR. The Committee noted that several sulfur compounds have been detected
in crude tall oil. These include sodium sulfate, hydrogen sulfide,
methyl mercaptan, dimethyl sulfide and dimethyl disulfide. However, it is
unlikely that the four latter compounds, which are volatile, would be retained
during the harsh conditions of subsequent refining and purification. The most
likely residual sulfur compounds in TOR would be sodium sulfate with possible
traces of dimethyl sulfide and dimethyl disulfide. However, there are
no data to confirm the identity of the sulfur compounds and whether their
presence in trace amounts would pose any toxicological concern.
In its previous evaluation of GEWR, the Committee concluded that GEWR
is not genotoxic in several in vitro test systems.
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