Safety evaluation of certain food additives - ipcs inchem

FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS 509
11. No such changes were seen in the corresponding females or in the low dietary
exposure level males or females. Males and females in the high dietary exposure
group showed a significant reduction in food intake when compared with controls.
Haematological, clinical biochemical and urinary analyses revealed no differences
between test groups and controls. Macroscopic pathology revealed no significant
lesions that could be associated with administration of the test substance.
Measurement of relative organ weights revealed non-dose-related increases in the
relative right kidney weight of males in the 35 mg/kg bw per day group and females
in the 175 mg/kg bw per day group and the relative right gonad weight of males in
the 175 mg/kg bw per day group. The authors stated that most of the organ weight
differences were inconsistent as to occurrence, sex and unilateral involvement of
bilateral organs and that it was difficult to ascertain whether they represented
treatment-related effects. In the absence of a clear dose–response relationship, the
changes cannot be associated with administration of the test substance. No
abnormal histopathology was observed in either sex of rat at any dietary level.
Based on these results, the NOEL for rats maintained on diets designed to provide
isobutyl 3-(2-furan)propionate at doses of 35, 175 and 875 mg/kg bw per day for up
to 90 days was 875 mg/kg bw per day (Lough et al., 1985).
(e) 2-Phenyl-3-(2-furyl)prop-2-enal (No. 1502)
Groups of 15 male and 15 female Sprague-Dawley-derived OFA rats 4–5
weeks of age were administered 2-phenyl-3-(2-furyl)prop-2-enal (purity not given)
at 0.87 mg/kg bw per day in olive oil via gavage 7 days per week for a period of 13
weeks. A concurrently maintained control was administered the vehicle substance.
Water and food were provided ad libitum. Animals were subject to daily examination
and observations of behaviour. Body weights for each rat and food consumption for
each cage of four animals were measured weekly. Haematology and serum
biochemistry were performed for eight males and eight females at weeks 4 (serum
biochemistry limited to blood urea nitrogen) and 13. At 13 weeks, 16 male and 16
female control and dosed rats were necropsied. The liver, kidneys, spleen, heart,
adrenal glands, testes and ovaries were weighed. Major tissue types were
preserved for histopathological examination.
Clinical examinations revealed no differences in the mortality, behaviour,
body weight gain or food consumption for either test group in comparison with the
corresponding group of control animals. Administration of 2-phenyl-3-(2-furyl)prop-2-enal
produced no haematological effect. At 13 weeks, serum biochemistry
revealed a decrease in the blood urea levels in male rats and a decrease in the
cholesterol levels in both sexes of treated animals; however, the fluctuations in
clinical chemistry values were reported to remain within the normal range of
variation. With the exception of findings reported to have likely occurred as a result
of gavage error, macroscopic examination showed no lesions attributable to the
administration of the test substance. Organ weights were comparable between test
and control groups, and histological examination revealed no evidence of alterations
that could be related to administration of 2-phenyl-3-(2-furyl)prop-2-enal (Long,
1977b).