Safety evaluation of certain food additives - ipcs inchem

HYDROXY- AND ALKOXY-SUBSTITUTED BENZYL DERIVATIVES (addendum) 543
Table 3. Data summary of plasma elimination kinetics in rats administered
sodium [ 14 C]4-methoxybenzoyloxyacetate (No. 1880) intravenously and orally
via gavage (de Bie, 1999)
Parameter Intravenous
(49 mg/kg bw)
2.3.2 Toxicological studies
(a) Acute toxicity
No additional acute toxicity studies for these agents have been reported
since the submission of the original monograph (Annex 1, reference 154).
(b) Short-term studies of toxicity
Oral, not
pretreated (508
mg/kg bw)
Tmax (h) – 0.5 0.5
Cmax (μg/g) 110.2 440 414
First phase t½ (min) 12 52 68
Terminal t½ (h) 8.3 3.8 3.4
Volume of distribution (l) 7.2 2.8 2.8
Total clearance (ml/min) 10.0 8.5 9.8
Mean residence time (h) 1.1 1.8 1.9
AUC0–24 h (mg·h/l) 83.4 1042 904
AUC0– (mg·h/l) 84.2 1043 905
(i) Sodium 4-methoxybenzoyloxyacetate (No. 1880)
Oral, pretreated a
(530 mg/kg bw)
AUC, area under the concentration–time curve; Cmax, maximum plasma concentration; t½, halflife;
Tmax, time taken to reach maximum plasma concentration.
a Pretreatment consisted of a diet providing 1% sodium [ 14 C]4-methoxybenzoyloxyacetate for
2 weeks prior to delivering the 530 mg/kg bw dose by gavage.
In a 13-week study, four groups of Wistar rats (20 per sex per group) were
maintained on diets containing 0, 0.5, 1 or 2% sodium 4-methoxybenzoyloxyacetate
(No. 1880). These dietary intake levels correspond to estimated daily intake levels
of 0, 340, 690 and 1400 mg/kg bw for males and 0, 390, 810 and 1600 mg/kg bw
for females. Weekly measurement of body weight and food consumption and
calculation of efficiency of food utilization showed no difference between test
and control animals. Haematological examinations, blood chemistry determinations
and urinary analysis conducted at week 13 showed normal values when compared
with controls. At necropsy, there were no significant differences in relative and
absolute organ weights between test and control groups. Histopathological analysis
of the stomach revealed mild hyperplasia and hyperkeratosis of the squamous
epithelium of the limiting ridge in some animals of the mid- and high-dose groups.