Safety evaluation of certain food additives - ipcs inchem

504 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
1502), one study with a furan-substituted aliphatic ester (No. 1514), one study with
a furan-substituted ether (No. 1520) and one study with a furan-substituted thioester
(No. 1526). In addition, two studies are available for the products formed when
thioesters (Nos 1525 and 1526) are hydrolysed in vivo.
(a) 2-Pentylfuran (No. 1491)
Sprague-Dawley albino rats (23 per sex per group) were maintained on a
diet calculated to provide an average daily intake of 2-pentylfuran (purity not given)
at 25.6 or 26.0 mg/kg bw for males and females, respectively, for 13 weeks. Food
and water were provided ad libitum. Weekly measurement of body weights, food
consumption and food utilization revealed no differences between test and control
groups. Animals were observed daily for clinical signs of toxicity and behaviour.
During weeks 6 and 13, urinary analysis was performed on eight males and females
from each group. At week 6, eight males and females from each group were
sacrificed by exsanguination for haematological examination. The remaining 15
males and 15 females were sacrificed at the end of week 13. All animals were
necropsied and tissues examined for macroscopic lesions. The kidneys, liver,
spleen, heart and testes or ovaries were weighed. Major tissues, including brain,
pituitary, thyroid and salivary glands, lymph nodes (cervical and mesenteric), lung,
diaphragm, heart, liver, stomach, duodenum, pancreas, femur with marrow, small
intestine, large intestine, spleen, adrenals, kidney (transverse and longitudinal
sections), testes and anexa, ovaries, uterus, bladder, spinal cord (thoracic), skin
and any lesions were preserved in 10% buffered formalin and embedded in paraffin
blocks for histological evaluation. Haematological examination and urinary analysis
revealed no differences between test and control rats. Test group rats revealed a
statistically significant increase in serum alkaline phosphatase (ALP) levels
compared with controls at week 13. However, in control males, the value for serum
ALP level was 334 international units (IU) at week 6 and inexplicably dropped to
116 IU at week 13, whereas in control females, ALP concentration dropped from
346 to 120 IU from week 6 to week 13. Additionally, the author reported that serum
ALP levels were still within the normal range and thus were not considered
biologically significant. Some male and female animals showed lung tissue that was
mildly hyperaemic, a chronic respiratory condition common among this strain of rats.
The average liver weight for treated males was significantly greater than the liver
weights of control animals. Female rats revealed significant increases in liver and
kidney weights when compared with the control group. However, examination of
these organs revealed no evidence of histopathology (Shellenberger, 1971c).
Furthermore, the author stated that the organ weights for the control male and
female groups were significantly lower than those of control animals of the same
strain and age used in a variety of studies under the same conditions
(Shellenberger, 1971a). Based on lower control organ weights and the absence of
organ histopathology, the authors concluded that no effect could be attributed to the
administration of 2-pentylfuran in the diet of rats (Shellenberger, 1971b).