Safety evaluation of certain food additives - ipcs inchem

506 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
As reported above, two female rats administered 800 mg/kg bw per day died
or were moribund on day 1 of the study, and one female rat from the mid-dose (400
mg/kg bw per day) group was found dead on day 2. The cause of death for the middose
female could not be determined owing to the autolysis that had taken place
by the time of discovery. All other animals survived to the completion of the study.
Clinical signs observed included dehydration, decreased faeces (quantitative data
not provided), depressed general activity levels and sialorrhoea in mid- and highdose
(600 mg/kg bw per day) groups. The authors proposed that the sialorrhoea
may have been due to the taste of the test material.
The mean body weights of high-dose males were significantly lower than
those of control animals on days 4, 7, 14 and 21; although they were lower on day
28, the difference was not statistically significant. Mean body weights of high-dose
females were slightly lower than those of controls on days 1 and 4, but were higher
than those of controls from day 7 to termination of the study. The mean body weight
for mid-dose females was also higher on day 14 and onward when compared with
controls. For mid-dose males and low-dose males and females, mean body weights
were comparable with those of controls.
Feed consumption in male and female rats was significantly lower (74%) on
day 4 for the high-dose group that received 600 mg/kg bw per day when compared
with the day 4 controls. Mean feed consumption was also significantly decreased
for the high-dose males on day 7. High-dose female rats showed increased feed
consumption compared with controls on day 7, which reached statistical
significance on days 21 through 28.
High-dose males showed a significantly lower mean haematocrit and
increased mean corpuscular haemoglobin concentrations. Lower mean red blood
cell counts were noted for high-dose males; however, they were not significant. Very
slightly lower mean haematocrit, erythrocyte count and haemoglobin concentrations
were noted for male rats in the low- and mid-dose groups; however, these changes
were not significant. Mid- and high-dose females showed a significant reduction in
mean red blood cell counts, mean haemoglobin concentrations and mean
haematocrit values, whereas low-dose females showed reduced values for these
parameters without statistical significance. The reduction in haematology values
indicates a loss of red blood cells. This most likely was due to gastric irritation, since
no other sites of possible haemorrhage were identified. Minimal poikilocytosis (a
common variant of erythrocyte morphology) was observed in 2/5 male rats from
each test group and in 1/5, 1/5, 1/5 and 2/5 female rats from the control, low-dose,
mid-dose and high-dose groups, respectively. Mean glucose levels were
significantly lower and mean sorbitol dehydrogenase (SDH) levels were higher for
high-dose males. One mid-dose male rat showed a significant increase in SDH level
when compared with controls. Mean SDH levels were significantly higher for highdose
females when compared with controls. Mean total protein levels were
significantly lower for male rats in the high- and low-dose groups. The mean albumin
levels and albumin/globulin ratios were significantly lower for low-dose males.
The mean relative kidney weights for the high- and mid-dose males were
higher compared with those of controls, but only the mid-dose group reached