FAO Nutrition Meetings
Report Series No. 48A
WHO/FOOD ADD/70.39
TOXICOLOGICAL EVALUATION OF SOME
EXTRACTION SOLVENTS AND CERTAIN
OTHER SUBSTANCES
The content of this document is the
result of the deliberations of the Joint
FAO/WHO Expert Committee on Food Additives
which met in Geneva, 24 June -2 July 19701
Food and Agriculture Organization of the United Nations
World Health Organization
1 Fourteenth report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series in press; Wld Hlth
Org. techn. Rep. Ser., in press.
ETHYL MALTOL
Biological data
Biochemical aspects
Oral administration of ethyl maltol is almost completely absorbed
from the gut. 65-70% appears in the urine as gluconomide or sulfate
within 2 hours. None was detected in the faeces (Gralla et al., 1969).
Acute toxicity
Animal Route LD50 References
(mg/kg
body weight)
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 body-weight of
ethyl maltol. 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 dilatation 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 ethyl maltol in oral
capsules at 0, 125, 250 and 500 mg/kg body-weight/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 ethyl maltol. Vomiting occurred at the
highest dose level (Gralla et al., 1969).
In another experiment four groups of 8 dogs each received orally
capsules containing ethyl maltol at 0, 50, 100 and 200 mg/kg
body-weight/day for 2 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 2 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 2 years on
diets containing ethyl maltol at the following dose levels: 0, 50, 100
and 200 mg/kg body-weight. 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, rate weight, survival,
urinalysis, haematology, clinical chemistry, tumour incidence,
gross-and histopathology (Gralla et al., 1969).
Special studies
Rat. Four groups of 20 rats given 0, 50, 100 and 200 mg/kg
bodyweight/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).
Comments
No data are available on the metabolic behaviour of ethyl maltol
and studies on this aspect would be desirable. 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 in the rat
0.4 per cent (= 4000 ppm) equivalent to 200 mg/kg bodyweight in the
rat.
Estimate of acceptable daily intake for man
mg/kg body-weight
Unconditional acceptance 0-2
REFERENCES
Gralla, E. et al. (1969) Toxicol. Appl. Pharmacol., 15, 604.