ACESULFAME POTASSIUM*
Explanation
Acesulfame K was evaluated by the Joint FAO/WHO Expert Committee
on Food Additives in 1981 (see Annex I, Ref. 57). Some shortcomings
were apparent in the long-term/carcinogenicity studies in the mouse
and rat and no ADI for man was allocated. A toxicological monograph
was prepared (see Annex I, Ref. 58).
Since that evaluation, additional studies have become available
and are summarized and discussed in the following monograph addendum.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Absorption, distribution and excretion
Single oral doses of approximately 15 mg 14C-acesulfame K/kg bw
were administered to male and female rats which had been pretreated
with unlabelled Acesulfame K at a level of 300 mg/kg diet for 60 days.
Control animals without pretreatment were also similarly dosed with
14C-acesulfame K. In all animals 95.1-98.2% of the dose was recovered
in urine and cage washings, and 0.95-2.86% in faeces. Total recoveries
were 96.3-99.2%. Excretion of radioactivity was rapid, 92.6-96.8% of
the dose being excreted within 24 hours and displayed biphasic
kinetics. The half-life of the rapid phase was 4-4.5 hours and for the
slower phase (accounting for <0.5% of the dose) was 109-257 hours.
No significant differences in route or rate of excretion were
observed between sexes nor between controls and animals pretreated
with Acesulfame K for 60 days (Volz & Eckert, 1981).
Biotransformation
Separation by TLC of urinary extracts from rats used in the above
study revealed only one peak which was identical with Acesulfame K. No
metabolites were detected in control or Acesulfame K-pretreated
animals (Volz & Eckert, 1981).
* Monograph addendum.
TOXICOLOGICAL STUDIES
Special studies on DNA binding
After pretreatment for seven days with a diet containing 3%
Acesulfame K, male rats were given a dose of 250 mg Acesulfame K
containing 14C-acesulfame K (9.6 x 108 dpm) by oral gavage. After
eight hours the animals were killed and liver and spleen excised; DNA
and chromatin protein was isolated from these organs. No radioactivity
could be detected on any DNA sample. A low level of activity
(8-11 dpm/mg protein) was associated with chromatin protein and this
was claimed to be due to non-covalent interactions of unchanged
Acesulfame K (Sagelsdorff et al., 1981).
Special studies on nitrosation of Acesulfame K
Acesulfame K was incubated at 37°C with excess NaNO2
(276 mg/100 ml) at pH 3 and pH 1 for one hour and four hours. The
maximum yield of N-nitroso derivative was 1.4 x 10-3% after four
hours at pH 1. This was considered to represent a negligible hazard
in vivo (Eisenbrand, 1982).
Special studies on the possible reactions of Acesulfame K with food
constituents
Acesulfame K (1% aqueous solutions) was heated at 100°C with the
model food constituents, ethanol, sorbitol, glycine, alanine, glutamic
acid, phenyl alanine or n-butylamine, in acetate buffer at pH 5.
Analysis by HPLC and UV-spectrometry failed to detect any
decomposition or interaction products of Acesulfame K in any of the
model systems (Clauss, 1981).
Long-term studies
Rat
In the previous evaluation, it was observed that some
shortcomings were apparent in the second long-term feeding study in
rats, in that only a small proportion of the animals in the control
and top-dose (3% Acesulfame K) groups were examined histopatho-
logically in detail. A detailed histopathological examination has now
been performed on the remaining animals in the control and top-dose
groups, and on all animals in the lower (0.3% and 1%) dose groups.
It was concluded that there were no treatment-related histopathological
changes and, in particular, no evidence of an increase in the incidence
or alteration of the biological type of the neoplasms diagnosed
(Newman, 1982).
Comments
The absence of mutagenic activity in several in vitro and
in vivo assays together with negative results in the two-year study
in rats indicate that Acesulfame K is devoid of mutagenic/carcinogenic
activity. The earlier mouse carcinogenicity study, though not meeting
current requirements, was also negative.
EVALUATION
Level causing no toxicological effect
Rat: 3% (30 000 ppm) in the diet, equal to 3-1.5 g/kg bw.
Dog: 3% (30 000 ppm) in the diet, equal to 900 mg/kg bw.
Estimate of acceptable daily intake for man
0-9 mg/kg bw.
REFERENCES
Clauss (1981) Model experiments aimed at detecting possible reactions
of Acesulfame K with constituents of food. Unpublished report
submitted to WHO by Hoechst A.G.
Eisenbrand, G. (1982) The nitrosatability of Acesulfame potassium in
the nitrosamine assay procedure of WHO. Unpublished report
submitted to WHO by Hoechst A.G.
Newman, A. J. (1982) Pathology report of the combined chronic toxicity
and carcinogenicity study with Acesulfame K in rats. Unpublished
report submitted to WHO by Hoechst A.G.
Sagelsdorff, P., Lutz, W. K, & Schlatter, Ch. (1981) Research Report
No. 40182A. Unpublished report submitted to WHO by Hoechst A.G.
Volz, M. & Eckert (1981) Research Report No. 01-L42-0352-81.
Unpublished report submitted to WHO by Hoechst A.G.