Safety evaluation of certain food additives - ipcs inchem

FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS 523
substance. The authors concluded that 2-furyl methyl ketone exhibits only mild
clastogenic activity in mouse bone marrow and is not clastogenic in germ cells
(Sujatha et al., 1993).
2-Furyl methyl ketone was evaluated for induction of sister chromatid
exchanges (SCE) in bone marrow of female Swiss albino mice. Groups of two per
dose per exposure regimen were administered compound (99% pure) at 0, 1000,
2000 or 3000 mg/l via gavage either once or for 5 consecutive days. 5-
Bromodeoxyuridine was injected intraperitoneally to label chromatids. The mice
were sacrificed at 12, 24 or 48 h after receiving the last dose, and slides of bone
marrow were prepared and processed for differential staining. A dose-related
increase up to about 2-fold in SCE was observed for the 12- and 24-h groups of
both the single-dose regimen and the multiple-dose regimen (Sujatha, 2007).
2-Furyl methyl ketone was evaluated for induction of UDS in hepatocytes
isolated from livers of dosed male Sprague-Dawley rats. The assay was conducted
according to Good Laboratory Practices and OECD guidelines. In a preliminary
range-finding toxicity study, lethality was observed at 30 mg/kg bw and greater, and
signs of toxicity were observed at 20 mg/kg bw. No sex differences were observed,
and therefore only males were used in the main study. Groups of four rats were
administered compound (purity not given) at 0, 7 or 21 mg/kg bw via gavage. In
experiment 1, the hepatocytes were isolated 16 h post-dosing; in experiment 2,
hepatocytes were isolated 2 h post-dosing and cultured for autoradiographic
measurement of UDS. No UDS was observed in either experiment, in contrast to
the positive controls 2-acetylaminofluorene and N,N-dimethylhydrazine (Durward,
2007b).
O-Ethyl S-(2-furylmethyl)thiocarbonate (No. 1526) was evaluated for
induction of micronuclei in bone marrow erythrocytes of NMRI BR mice. Groups of
five per sex per dose per sampling time were administered single doses of
compound (99% pure) at 0 (vehicle control), 100, 250 or 500 mg/kg bw in corn oil
via gavage. Dosed animals at every dose level and controls were killed at 24 h postdosing.
Additionally, a second group of high-dose mice (i.e. 500 mg/kg bw) and the
positive control (cyclophosphamide) group were terminated at 48 h post-dosing.
Bone marrow smears were prepared from the femurs. No increase in the incidence
of micronucleated polychromatic erythrocytes was observed in dosed mice
compared with controls, in contrast to the positive control, which induced a 20-fold
increase. However, the authors also noted that cells obtained from dosed animals
did not exhibit a reduction in the ratio of polychromatic to normochromatic
erythrocytes, indicating an absence of toxicity, which could be due to lack of
adequate exposure of bone marrow (Verspeek-Rip, 2001).
(c) Conclusions
With few exceptions, eight representative substances of this group were
consistently negative in mutation assays conducted in various strains of S.
typhimurium and E. coli under appropriate testing conditions. Negative and positive
results were obtained in the rec assay in B. subtilis for 2-methylfuran and 2,5dimethylfuran.
In mammalian genotoxicity assays conducted in CHO and V79 cells