Safety evaluation of certain food additives - ipcs inchem

522 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
24- or 48-h exposure period, O-ethyl-S-(2-furylmethyl)thiocarbonate (up to 280 μg/
ml) also induced dose-dependent and statistically significant increases in the
number of chromosomal aberrations in the absence of metabolic activation in
comparison with a negative control (Meerts, 2000).
(b) In vivo
As reported in an abstract, 2-methylfuran (No. 1487) (purity not given) did
not induce chromosomal aberrations in bone marrow cells or spermatocytes of
Swiss albino mice evaluated at 24-h intervals following administration in the diet at
concentrations of 1000, 2000 or 4000 mg/kg (approximately 100, 200 and 400 mg/
kg bw per day, respectively) for a period of 5 days. No positive control was included.
Moreover, the authors noted that 2-methylfuran did not inhibit spindle protein
synthesis or cell division in the somatic cells. In the germ cells, which were evaluated
at weekly intervals for a period of 5 weeks following final dosing, in order to cover
one full spermatogenesis cycle, no structural sperm-head abnormalities were
reported (Subramanyam et al., 1989).
2-Furyl methyl ketone (No. 1503) was evaluated for clastogenic activity in
bone marrow and germ cells of Swiss albino mice. Groups of two per dose per
sampling time were administered the compound (99% pure) orally at 0 (control),
1000, 2000 or 3000 mg/l in 0.5 ml of water (approximately 0, 20, 40 and 60 mg/kg
bw, respectively) either as a single dose or once daily for 5 consecutive days. No
positive control was included. Bone marrow cells were collected periodically for up
to 72 h following dosing, and meiotic and sperm preparations from testes and
epididymis, respectively, were assessed at 24 h and weekly for a total of 5 weeks
post-dosing. In bone marrow cells, the substance at the high dose level was
observed to inhibit mitosis beginning at 18 h following single- or multiple-dose
treatment. At 24 h, mitodepression was also observed at the high dose level in the
single-dose experiment, as well as at the middle and high dose levels in mice
administered multiple doses. In the repeat-dose test protocol, the effect remained
significant for up to 36 h post-treatment. Mitodepression was accompanied by
increases in the frequency of structural chromosomal aberrations, mainly gaps
and breaks, in the bone marrow cells. Specifically, at the high dose level (i.e. 3000
mg/l), between 18 and 24 h following single-dose administration and 12 and 48 h
following final treatment of multiple-dose groups, the frequency of aberrations was
elevated. Additionally, in animals receiving multiple doses of 2-furyl methyl ketone,
significant increases in the number of chromosomal aberrations were also observed
at the middle dose level (i.e. 2000 mg/l) between 24 and 36 h post-treatment. In
contrast to the dose- and time-dependent increase in chromosomal aberrations in
the somatic cells, only a single isolated increase in structural chromosomal
aberrations was observed in mouse spermatocytes 3 weeks following single-dose
administrations of the substance, and only at the highest dose level. Following
multiple-dose administration, abnormalities in germ cells were limited to significant
increases in polyploidy and XY univalents occurring at weeks 3 and 4 at the highest
dose level. Furthermore, no sperm-head abnormalities were observed at any dose
level, irrespective of the treatment protocol. The absence of sperm-head
abnormalities at all dose levels was indicative of a lack of sperm toxicity of the