Safety evaluation of certain food additives

No treatment-related effects were observed at necropsy or during
histopathological examination. In males, group mean absolute kidney weights were
statistically significantly reduced in the 10 000 mg/kg feed (–8%), 50 000 mg/kg feed
(–15%) and 1000 mg/kg bw per day (–7%) groups, but group mean relative kidney
weights were not affected. In females, in contrast, no changes were observed in
group mean absolute kidney weights, whereas the group mean relative kidney
weight was statistically significantly increased (+11%) in the 50 000 mg/kg feed
group. These inconsistent changes were not considered to be treatment related,
given also the absence of histopathological changes in the kidneys.
Overall, it can be concluded that, in the absence of dose relationships and
histopathological findings, the effects observed were of no toxicological relevance.
The no-observed-adverse-effect level (NOAEL) was 50 000 mg/kg feed, equal to
4590 mg/kg bw per day, the highest dose tested (Zühlke, 1990).
In a limitedly reported 30-day study of toxicity, groups of 10 male and 10
female SD rats were administered cassia gum via the diet at levels corre-
sponding to intakes of 0, 250, 500 and 1000 mg/kg bw per day. Statements
regarding compliance with GLP and QA were lacking. No treatment-related
effects on mortality, body weight gain, food consumption or food utilization were
observed. The investigated haematological (red and white blood cell counts,
haemoglobin) and biochemical parameters (albumin, cholesterol, creatinine,
alanine aminotransferase, aspartate aminotransferase, glucose, total protein,
triglyceride and urea nitrogen) were not affected. No gross findings were observed,
and investigated organ weights (liver, kidney, spleen, ovaries and testes) were not
affected. Histopathological examination of liver, kidney, spleen, stomach and
intestines, ovaries and testes also did not show treatment-related effects. It seems,
therefore, that no adverse effects were observed at doses up to and including 1000
mg/kg bw per day, the highest dose tested (Weidu, 2006).
Groups of four male and four female Beagle dogs were given semi-refined
cassia gum mixed into canned dog food at a dietary concentration of 7500 or
25 000 mg/kg for 90 days (equal to doses of 980 and 3290 mg/kg bw per day for
males and 1130 and 3890 mg/kg bw per day for females). A control group of the
same size was administered the canned dog food with 2300 mg/kg locust (carob)
bean gum. The study was essentially performed as described in OECD Test
Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents) and
was certified for compliance with GLP and QA. The only treatment-related effect
observed was a dose-dependent increase in water consumption. However, as this
was most likely associated with water retention in the gastrointestinal tract by
colloidally dissolved semi-refined cassia gum, it was not considered to be of
toxicological relevance. All other effects observed (for several haematological,
blood coagulation and biochemical parameters and some organ weights) were not
considered treatment related because they lacked a dose or time relationship,
occurred in one sex only and/or remained within the historical reference range.
Overall, it can be concluded that the NOAEL was 25 000 mg/kg feed, equal to
3290 mg/kg bw per day, the highest dose tested (Schuh, 1990).

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