Safety evaluation of certain food additives - ipcs inchem

544 HYDROXY- AND ALKOXY-SUBSTITUTED BENZYL DERIVATIVES (addendum)
Further, there was slight hyperplasia of the urinary bladder epithelium in part of the
highest dose group. Based on these data, the no-observed-adverse-effect level
(NOAEL) was determined to be 0.5% (340 and 390 mg/kg bw per day for males and
females, respectively) (see Table 4) (Lina, 1999).
Table 4. Results of short-term studies of toxicity with hydroxy- and alkoxysubstituted
benzyl derivatives used as flavouring agents
No. Flavouring agent Species;
sex
1880 Sodium 4methoxybenzoyloxyacetate
No. of
test
groups a /
no. per
group b
Route Duration
(days)
NOAEL
(mg/kg
bw per
day)
Rat; M, F 3/40 Diet 91 M: 340
F: 390
F, female; M, male.
a Total number of test groups does not include control animals.
b Total number per test group includes both male and female animals.
(c) Genotoxicity
Reference
Lina (1999)
No mutagenic activity was observed when Salmonella typhimurium strains
TA98, TA100, TA1535 and TA1537 were incubated with up to 5000 μg of vanillin
3-(l-menthoxy)propane-1,2-diol acetal (No. 1879) or sodium 4-methoxybenzoyloxyacetate
(No. 1880) per plate, with and without metabolic activation (Kajiura,
1996; Van Delft, 1998b).
Similarly, no mutagenic activity was observed when 0–5000 μg divanillin
(No. 1881)/plate was incubated with S. typhimurium strains TA98, TA100, TA102,
TA1535 and TA1537, with and without metabolic activation, in two replicate studies
(King, 2002). At 1500 and 5000 μg/plate, precipitation was observed (King, 2002).
No mutagenic activity was observed when up to 5000 μg vanillin 3-(lmenthoxy)propane-1,2-diol
acetal (No. 1879)/plate was incubated with Escherichia
coli WP2uvrA in the presence or absence of metabolic activation (Kajiura, 1996).
No mutagenic activity was observed in the mouse lymphoma forward
mutation assay when cultured mouse lymphoma L5178Y cells were exposed to up
to 0, 1.2, 2.4, 3.2, 4.2, 5.6, 7.5 or 10 mmol sodium 4-methoxybenzoyloxyacetate
(No. 1880)/l (0, 278, 557, 743, 975, 1300, 1741 or 2321 μg/ml), with and without S9
metabolic activation. Negative results were seen in a second trial of the assay with
0, 0.625, 1.25, 2.5, 5.0 or 10.0 mmol sodium 4-methoxybenzoyloxyacetate/l (0, 145,
290, 580, 1161 or 2321 μg/ml) (Van Delft, 1998a).
There was no indication of mutagenicity in a chromosomal aberration test
when Chinese hamster ovary cells were incubated for 18 h and fixed for 18 h with
0, 0.1, 0.3, 0.6, 1.2, 2.4, 4.8 or 9.6 10 mmol sodium 4-methoxybenzoyloxyacetate/l
(0, 23, 70, 139, 279, 557, 1114 or 2228 μg/ml) with S9 metabolic activation. In a trial