Safety evaluation of certain food additives - ipcs inchem

FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS 507
statistical significance. The mean absolute and relative kidney weights for high-dose
female rats were significantly greater than those of controls. Clinical chemistry did
not indicate nephrotoxicity related to administration of the test material. The mean
absolute and relative liver weights were significantly increased for the mid- and highdose
male and female groups. Relative thymus weights for the high-dose males
were significantly increased; however, this was considered to be reflective of lower
terminal body weights for this group rather than related to test substance
administration. No macroscopic pathology was related to treatment according to the
authors of the study.
Treatment-related histopathology noted for mid- and high-dose males
included hyperkeratosis (5/5) and acanthosis (5/5) of the non-glandular stomach
(forestomach) mucosa, hypertrophy of hepatocytes (4/5 for the mid-dose group and
4/5 for the high-dose group) and an increased number of hepatocytes with enlarged
nuclei (4/5 for the mid-dose group and 5/5 for the high-dose group). Females
revealed hyperkeratosis and acanthosis of the non-glandular stomach mucosa,
hypertrophy of the hepatocytes and increased number of hepatocytes with enlarged
nuclei (4/4 for the mid-dose group and 5/5 for the high-dose group). Hypertrophy of
hepatocytes (1/5) and increased number of hepatocytes with enlarged nuclei (1/5)
were observed for low-dose female rats. The test material was a strong gastric
irritant, which accounts for the hyperkeratosis and acanthosis of the non-glandular
stomach mucosa observed in mid- and high-dose rats. The study pathologist
concluded that hypertrophy of the hepatocytes and enlarged nuclei of hepatocytes
were considered adaptive responses to the influx of large amounts of 3-(2-furyl)acrolein
via gavage to compensate for increased metabolic activity, not to any
toxicity related to the test substance. The authors concluded that the no-observedadverse-effect
level (NOAEL) for 3-(2-furyl)acrolein was 100 mg/kg bw per day in
rats (Faber & Hosenfeld, 1992).
(d) 3-(2-Furyl)acrolein (No. 1497), 2-furyl methyl ketone (No. 1503) and
isobutyl 3-(2-furan)propionate (No. 1514)
In a subchronic study, Sprague-Dawley rats were allocated into groups of 32
per sex for the control and low dietary intake level, 12 per sex for the mid-range
group and 10 per sex for the high-intake group. The rats were maintained on diets
calculated to provide 3-(2-furyl)acrolein at 0, 5, 45 or 405 mg/kg bw per day, 2-furyl
methyl ketone at 0, 5, 25 or 100 mg/kg bw per day or isobutyl 3-(2-furan)propionate
at 0, 35, 175 or 875 mg/kg bw per day for 28 days. The animals were provided ad
libitum access to food and water throughout the study. Animals were observed daily
for clinical manifestations of toxicity and changes in behaviour. Body weights and
food consumption were recorded weekly. Haematology, blood chemistry and
urinary analyses were conducted at 4 weeks. At the end of 28 days, all of the high
intake level rats and 16 per sex of the control and low intake level rats were sacrificed
by ether anaesthesia and subsequent exsanguination. The remaining animals
continued on test for 90 days.
In the 3-(2-furyl)acrolein study, a significant decrease in body weight gain
was noted for males and females in the 405 mg/kg bw per day dietary exposure
group when compared with controls at week 4. At the 45 mg/kg bw per day dietary