INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, ENZYMES, FLAVOUR
ENHANCERS, THICKENING AGENTS, AND
CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES 6
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
4-13 June 19741
World Health Organization Geneva 1975
1 Eighteenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
FAO Nutrition Meetings Report Series, 1974, No. 54.
ETHYLMALTOL
Explanation
This compound has been evaluated for acceptable daily intake by
the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 22) in 1970. No toxicological monograph has been published at
that time.
In the Fourteenth Report1 it was noted that ethylmaltol is
intended as an alternative to its homologue, meltol. Data were
sufficient to assign an acceptable daily intake of 0-2 mg/kg bw.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Orally administered ethylmaltol is almost completely absorbed
from the gut. 65-70% appears in the urine as glucuronide/or sulfate
within two hours. None was detected in the faeces (Gralla et al.,
1969). Following oral (200 mg/kg) and i.v. (10 mg/kg) administration
to dogs showed that orally given ethylmaltol is rapidly and
extensively absorbed from the gut. 65-70% are excreted in the
urine as sulfate and glucuronide after oral and 30-96% after i.v.
administration. Faecal excretion varied from 0.3-4% (Rennhard).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Rat
Four groups of 20 rats given 0, 50, 100 and 200 mg/kg bw/day were
mated after 90 days feeding for 18 days and allowed to produce a first
litter. After a rest period they were mated again for 18 days and
produced a second litter. No difference was seen between controls and
test animals as regards conception, litter size, survival of pups,
weight at weaning and teratology at 21 days of age (Gralla et al.,
1969).
1 Wld Hlth Org. techn. Rep. Ser., 1971, No. 462
Acute toxicity
LD50
Animal Route (mg/kg bw) References
Mouse Oral 780 Gralla et al., 1969
Rat Oral 1150 Gralla et al., 1969
Chick Oral 1270 Gralla et al., 1969
Short-term studies
Rat
Four groups of 10 male and 10 female rats were fed for 90 days on
diets containing 0, 250, 500 or 1000 mg/kg bw of ethylmaltol. No
abnormalities were detected with regard to survival, growth, organ
weight, haematology, urinalysis, gross- and histopathology with the
exception of some anaemia and icterus at the 250 mg/kg dose level.
There was slight depression of body weight only in females at the 500
and 1000 mg/kg level and very slight reduction at the 250 mg/kg level.
The only pathological abnormality was noted at the highest level and
consisted of dilation of the glomerular tuft with protein loss and
casts in Bowman's space and renal tubules (Gralla et al., 1969).
Dog
Four groups of beagles each received ethylmaltol in oral capsules
at 0, 125, 250 and 500 mg/kg bw/day for 90 days. No deleterious
effects were noted on mortality, body weight gain, haematology,
urinalysis, clinical chemistry and gross- and histopathology. Slight
icterus was noted in the serum of animals at the two highest levels
tested but this colour change may have been due to an iron complex
formed by ethylmaltol. Vomiting occurred at the highest dose level
(Gralla et al., 1969).
In another experiment four groups of eight dogs each received
orally capsules containing ethylmaltol at 0, 50, 100 and 200 mg/kg
bw/day for two years. No abnormalities were found as regards
mortality, body weight, organ weight, haematology, urinalysis,
clinical chemistry, gross- and histopathology except for slight
myeloid hyperplasia of the sternal marrow in two females at the
200 mg/kg level (Gralla et al., 1969).
Long-term studies
Rat
Groups of 25 male and female rats were fed for two years on diets
containing ethylmaltol at the following dose levels: 0, 50, 100 and
200 mg/kg bw. No abnormalities were seen as regards growth rate or
food consumption, urinalysis and haematology. Five male and five
female rats were sacrificed after one year and the remainder after two
years. There was no significant difference between controls and test
animals with respect to growth, organ weight, survival, urinalysis,
haematology, clinical chemistry, tumour incidence, gross- and
histopathology (Gralla et al., 1969).
Comments:
The metabolic data point to rapid absorption and excretion as
sulfate and glucuronide, Adequate two-year studies have been provided
in rat and dog in addition to a reproduction study in rats.
EVALUATION
Level causing no toxicological effect
Rat: 0.4% (=4000 ppm) in the diet equivalent to 200 mg/kg bw
Estimate of acceptable daily intake for man
0-2 mg/kg bw
REFERENCES
Gralla, E. et al. (1969) Toxicol. appl. Pharmacol., 15, 604
Rennhard, H. H. (1971) J. Agr. Food Chem., Vol. 19, 152