Safety evaluation of certain food additives - ipcs inchem

512 FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS
(j) Structurally related substance furfuryl mercaptan (No. 1072) 1
In a 13-week study, groups of 15 weanling Wistar rats of each sex were given
daily doses of 0 (vehicle control), 1, 3 or 30 mg furfuryl mercaptan (No. 1072)/kg bw
in corn oil by stomach tube for a period of 13 weeks (7 days per week). Additional
satellite groups of five rats per sex were administered daily doses of 0, 3 or 30 mg
furfuryl mercaptan/kg bw for periods of 2 or 6 weeks. Clinical observations were
performed daily. Body weights were measured initially on days 1, 6 and 9 and then
weekly up to week 12. Food and water intakes were measured 1 day prior to the
weight measurements.
At the highest dose level, a significant decrease in body weight gain
observed in both males and females beginning on days 6–9 and continuing until
study termination (12–16% final body weight reductions) was associated with a
significantly reduced food intake. Furthermore, several differences in organ weights
were observed in high-dose animals (i.e. 30 mg/kg bw per day) at the conclusion of
the study. Significant organ weight differences, primarily consisting of reductions in
absolute organ weights and increases in relative organ weights (i.e. brain, kidneys,
stomach, small intestine, caecum, adrenals and gonads in males, and brain, heart,
liver, kidneys, stomach, caecum, adrenals and thyroid in females) were reported for
the 30 mg/kg bw per day group at 13 weeks and were thought to be associated with
the lower body weights. In addition to isolated organ weight changes in males and
females at the high-dose level in the satellite group terminated at week 6, increased
relative heart weights in males and reduced relative kidney weights in females were
reported for the group at the 3 mg/kg bw per day dose level. These changes were
not present in the 13-week group at the mid-dose level (i.e. 3 mg/kg bw per day)
and as such were considered to be unrelated to the administration of the test
substance. Urinary analysis, including concentration and dilution tests, performed
on the last day of treatment revealed no significant differences between test and
control groups. Likewise, no significant variations were observed in clinical
chemistry values. In high-dose males, statistically significant variations in
haematological parameters included increased packed cell volume and total
leukocyte counts at week 6 and increases in haemoglobin concentration and packed
cell volume at study termination; however, these changes were not considered to
represent a toxicologically significant adverse effect. At study termination,
macroscopic and microscopic examinations showed no lesions related to the
administration of the test substance. Based on organ weight changes confined to
the highest dose group, the authors concluded that 3 mg/kg bw per day was the
NOAEL (Phillips et al., 1977).
2.2.3 Genotoxicity studies
Genotoxicity testing has been performed on eight (Nos 1487, 1488, 1494,
1497, 1503, 1511, 1513 and 1526) representative furan-substituted aliphatic
hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters,
sulfides, disulfides and ethers in this group. The results of these tests are
summarized in Table 4 and described below.
1 Furfuryl mercaptan (No. 1072) is the principal hydrolysis product of O-ethyl S-(2-furylmethyl)thiocarbonate
(No. 1526).