Safety evaluation of certain food additives - ipcs inchem

496 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
In the same study, mice were injected intraperitoneally with 70 mg 2acetylfuran
(commercial grade)/kg bw in 0.9% sodium chloride, with and without
phenobarbital pretreatment, and 80 mg 2-acetylfuran/kg bw, with and without
cobalt(II) chloride pretreatment. The mortality rates were 1/12, 0/12, 0/12 and 0/12
for the 70 mg 2-acetylfuran/kg bw, 70 mg 2-acetylfuran/kg bw plus phenobarbital,
80 mg 2-acetylfuran/kg bw, and 80 mg 2-acetylfuran/kg bw plus cobalt(II) chloride
treatment groups, respectively. Mice treated with 2-acetylfuran showed no evidence
of toxicity in the kidneys. Hepatic necrosis, described as midzonal-centrilobular
necrosis of the parenchymal hepatocytes, was mild in severity with cobalt(II)
chloride pretreatment, showing a marked decrease in the incidence and severity of
necrosis.
Ten male ICR mice were injected intraperitoneally with 2-ethylfuran
(analytical reagent grade) at 2.6 mmol/kg bw (250 mg/kg bw) in sesame oil.
Histopathology of tissues collected 24 h later revealed extensive proximal tubular
necrosis of the kidneys and focal hydroptic degeneration of the liver. Significant
increases in the plasma urea nitrogen level (approximately 5 times control level)
and GPT level were reported (Wiley et al., 1984).
Severe bronchiolar necrosis was reported when 2-ethylfuran (2.6 mmol/kg
bw or 250 mg/kg bw) in sesame oil was administered by intraperitoneal injection to
male ICR mice. Administration of 1.56 mmol 2-ethylfuran/kg bw (150 mg/kg bw) via
intraperitoneal injection to five male ICR mice showed approximately a doubling,
compared with control values, of the amount of [ 14 C]thymidine incorporation into
pulmonary DNA measured at 3 days after dosing, which indicates cell replication
and lung repair (Gammal et al., 1984).
In a study of the tumour-inhibiting properties of 2-heptylfuran (No. 1492),
increased cytosolic glutathione S-transferase activity was observed in tissue
preparations of the liver, forestomach and small bowel mucosa isolated from 7week-old
female A/J mice (five mice per group) that received doses of 12, 25, 50 or
80 μmol of 2-heptylfuran dissolved in cottonseed oil via gavage every other day for
a total of three doses. A 50 μmol dose of 2-heptylfuran showed a significant increase
in acid-soluble sulfhydryl levels, which is a good measure of GSH content in tissues,
in all four tissue types (liver, small bowel mucosa, forestomach and lung) when
compared with controls (Lam & Zheng, 1992).
The neurotoxic potential of 2,5-dimethylfuran (No. 1488) and a series of
hexane derivatives was evaluated using freshly prepared Schwann cells isolated
from the sciatic nerves of neonatal Sprague-Dawley rats that were incubated with
0.17, 0.33, 0.67, 1.33, 2.66, 5.33, 10.7 or 21.3 mmol 2,5-dimethylfuran/l (16.3, 31.7,
64.4, 127.9, 255.7, 512.4, 1028.6 and 2047.6 μg/ml, respectively) (Kamijima et al.,
1996). Compared with other hexane derivatives, dimethylfuran exhibited a high
potential to inhibit the incorporation of [ 3 H]thymidine into Schwann cell DNA, as
indicated by its low median effective concentration (EC50 value). Concentrations of
2,5-dimethylfuran of 5.33 mmol/l (512.4 μg/ml) and above induced cytotoxic
changes in Schwann cell morphology, including a loss of cell processes, rounding
of cell shape and detachment from the substratum. At concentrations of 5.33 mmol/
l (512.4 μg/ml) and above, 2,5-dimethylfuran completely inhibited the Schwann