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.
    

    See Also:
       Toxicological Abbreviations
       ETHYL MALTOL (JECFA Evaluation)