Safety evaluation of certain food additives - ipcs inchem

508 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
level, males showed decreased body weight gains at week 12. Decreases in body
weight gain were accompanied by decreased food intake, which may have been
related to the palatability of the test material. Animals at the two lower doses
exhibited inconsistent intervals of low food consumption. Haematological and
urinary analyses were comparable between test groups and control animals at 28
and 90 days. Blood chemistry analysis revealed significant decreases in ALP and
glucose levels for the 405 mg/kg bw per day group at 28 days. Necropsy revealed
no significant macroscopic pathology. At 28 days, the mean relative liver weights of
females in the high-exposure group were significantly increased. At 4 weeks, the
mean relative right and left kidney weights were increased for the 405 mg/kg bw per
day group, whereas after 13 weeks, mean relative right kidney weights were
increased for the 5 mg/kg bw per day male group and mean relative left kidney
weights were elevated for the low-exposure females. No increased kidney weights
or any other organ weights were observed in the 45 mg/kg bw per day group
compared with controls. These organ weight increases were not accompanied by
any evidence of macroscopic or microscopic pathology. The 45 mg/kg bw per day
dietary level for 90 days was considered to be the NOAEL for 3-(2-furyl)acrolein.
In the 2-furyl methyl ketone study, male and female rats in the 100 mg/kg bw
per day group showed decreased body weight gain at day 28. Males at week 13
and females at week 9 in the 25 mg/kg bw per day groups showed reduced body
weight gain compared with controls. These body weight changes corresponded in
part to changes in food consumption. Males and females in the 100 mg/kg bw per
day groups showed a significant decrease in food consumption. Females in the 5
and 25 mg/kg bw per day groups showed a significant decrease in food consumption
when compared with controls; however, the corresponding male groups did not
show decreased food consumption. At 4 weeks, male and female rats in the
100 mg/kg bw per day groups showed a significant increase in the blood urea
nitrogen level and significant decreases in glucose and ALP levels when compared
with controls. Macroscopic pathological examinations were comparable for control
animals and test animals. Male and female rats at the 100 mg/kg bw per day intake
level showed increased mean relative liver weights when compared with controls.
Absolute liver weights were comparable with those of controls, suggesting that lower
body weights in the high-dose group may have been partly responsible for the
observed increased relative liver weights. At treatment termination, mean absolute
and relative liver weights were comparable between the control and high-dose
groups. Rats at lower intake levels exhibited no significant difference in organ
weights compared with control animals. At 28 days, males receiving 100 mg/kg bw
per day showed increased right and left gonad weights, without similar findings for
the 5 and 25 mg/kg bw per day exposure groups after 90 days. No abnormal
histopathology accompanied any of the organ weight differences. The NOAEL for
dietary administration of 2-furyl methyl ketone to rats for 90 days was determined
to be 25 mg/kg bw per day.
In the isobutyl 3(2-furan)propionate study, the death of one low-dose female
was reported to be unrelated to the test compound. Males on the diet designed to
provide 175 or 875 mg/kg bw per day showed a significant reduction in body weight
gain at 28 days, which persisted for the 175 mg/kg bw per day group up to week