Safety evaluation of certain food additives

body weight (bw) by oral gavage in two doses at a 2-h interval. The oral median
lethal dose (LD
50
value) in this study was >5000 mg/kg bw. The study was certified
for compliance with Good Laboratory Practice (GLP) and quality assurance (QA)
(Schöbel, 1986). In another limit test, 10 male and 10 female KM mice were given
in total 10 000 mg cassia gum/kg bw by oral gavage in four doses over 24 h. The
oral LD
50
value in this study was >10 000 mg/kg bw. Statements regarding
compliance with GLP and QA were lacking (Weidu, 2006).
2.2.2 Short-term studies of toxicity
In a 28-day study of toxicity (Zühlke, 1990), groups of five male and five
female Crl:CD (SD)BR Sprague-Dawley rats (aged 5–6 weeks) were administered
semi-refined cassia gum at dietary concentrations of 0, 2500, 10 000, 25 000 or
50 000 mg/kg feed (equal to doses of 0, 250, 1030, 2590 and 4960 mg/kg bw per
day for males and 0, 230, 1110, 2360 and 4590 mg/kg bw per day for females). A
sixth group received semi-refined cassia gum by gavage (in distilled water) 2 times
a day, at a total dose of 1000 mg/kg bw per day. The study was certified for
compliance with GLP and QA and was essentially performed as described in
Organisation for Economic Co-operation and Development (OECD) Test Guideline
407 (Repeated Dose 28-day Oral Toxicity Study in Rodents), although weekly
detailed clinical investigations and measurements of sensory reactivity were
omitted. Observations included mortality, clinical signs, behaviour, body weight,
food consumption, haematology, clinical chemistry, organ weights (adrenals, brain,
heart, kidneys, liver, ovaries and testes), macroscopic examination and
histopathology (on major organs of the animals in the control group, the 50 000 mg/
kg feed group and the group treated by gavage).
Five animals died during the experiment, but these deaths were incidental
or due to an intubation error or blood sampling procedure and were not
accompanied by signs of systemic target organ toxicity. No clinical changes that
could be attributed to the treatment were observed. Body weight gain was
statistically significantly reduced (–20%) in males of the 50 000 mg/kg feed group,
possibly related to a small (–11%) decrease in food intake in these animals. In
females, body weight gain was statistically significantly reduced (–17%) in the
10 000 and 25 000 mg/kg feed group and in the 1000 mg/kg bw per day group.
These changes are considered to be related to the viscous nature of cassia gum
and not considered to be of toxicological relevance.
Haematology and clinical chemistry findings included several statistically
significant changes that for the most part were small, were not dose related or
occurred in one sex only. They were also claimed to be within the normal range for
the species tested, but historical control data were not provided. The only changes
that were outside the historical control range and could have been related to
treatment were increased mean concentrations of glucose and triglyceride in both
sexes of the 10 000 mg/kg feed group (males 41% and 149% and females 56% and
46%, respectively) and 25 000 mg/kg feed group (males 53% and 168% and
females 74% and 67%, respectively). These findings were not dose related,
however, as they were not observed in the 50 000 mg/kg feed group or in the group
treated by gavage.

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