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

    See Also:
       Toxicological Abbreviations