WHO Food Additives Series, 1972, No. 4


    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Geneva,
    4-12 April 19721

    World Health Organization


    1 Sixteenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 505; FAO
    Nutrition Meetings Report Series, 1972, No. 51.


    Propyl, octyl and dodecyl gallates have previously been evaluated in
    the Sixth and Eighth Report of the Joint FAO/WHO Expert Committee.

    Additional Biological Data

    Acute toxicity


    Animal         Route          LD50        Vehicle      Reference
                             (Mg/kg body wt.) 

    Rat (male)     oral           2710        corn oil     Brun, 1970
    Rat (female)    "             1960            "             "
    Rat (male)      "             2710        water             "
    Rat (female)    "             2330            "             "

    Short-term studies


    Groups each of 20 rats (equally divided by sex) were maintained on
    diets containing 0, 1000, 2500 and 5000 ppm of octyl gallate for 13
    weeks.  All groups showed normal weight gains, food consumption.
    Haematologic and blood chemistry and urine analyses were normal.  A
    complete gross and histopathologic examination showed no compound
    related effects (Hazleton Lab. Inc. 1969a).


    Groups each of eight dogs (equally divided by sex) were fed diets
    containing 0, 0.1, 0.3 n-octyl gallate for 90 days, and 1.0% for four
    weeks, then reduced to 0.6% for the remainder of the study.  All
    groups showed normal weight gains, food consumption (except 1.0%
    group).  Haematologic and blood chemistry and urine analyses were
    normal.  A complete gross and histopathologic examination showed no
    compound related effects (Industrial Biotest Lab., 1970).  In another
    study groups each of eight dogs (equally divided by sex), were
    maintained on diets containing 0, 0.1, 0.25 or 0.5% octyl gallate for
    13 weeks.  All animals showed normal food consumption and weight gain.
    Haematologic and urine analyses were similar for test and control
    animals.  SGOT was slightly elevated in the 0.5% group.  Gross and
    histopathologic examination of tissues and organs showed no compound
    related effects (Hazleton Lab. Inc. 1969b).

    Long-term studies


    n-Octyl gallate was fed in the diet to groups of eight male and 16
    female rats for two successive generations at levels of 0, 0.1 or 0.3%
    (and 0.6% for one generation).  Rats were mated to produce two litters
    per generation with next generation selected from weanlings of the
    second litter.  A dietary level of 0.1% (1000 ppm) had no effect on
    reproduction performance or the offsprings.  At 0.3 and 0.6% dietary
    octyl gallate, there was no significant effect on the rat foetuses
    during pregnancy, but a marked effect was observed on survival through
    weaning.  In the case of the 0.6% group, return to normal diet for six
    weeks, prior to a third breeding, did not result in increased survival
    of offsprings through weaning (Industrial Biotest Lab., 1970).

    Groups each of 10 male and 20 female rats were maintained on diets
    containing 0, 1000 or 5000 ppm of octyl gallate.  The animals were
    bred twice for the first generation, and three times for the second
    generation.  At the time of weaning of the B1B litters, the 5000 ppm
    level was replaced by a 2500 ppm level for the second generation.  In
    the case of the second generation approximately 24 hours after birth,
    selected litters were redistributed to female parents so that control
    females nursed pups from test animals, and test animals nursed pups
    from control and other test groups.  One half P2 females bred for the
    third time (F2c) were examined by Caesarean section at time of
    delivery and the number of implantation sites, corpora lutes and
    foetuses determined.  One half the pups from each litter were examined
    for skeletal abnormalities, and the other half for visceral
    abnormalities.  The other parameters measured in this study were
    appearance, behaviour, growth of pups during the nursing and weaning
    process, fertility index, gestation index, live birth index, weaning
    survival index.  Autopsies were carried out on F2b weanling pups,
    (control suckled by control, each group suckled by respective group
    parent), as well as a microscopic examination of pituitary, thyroid,
    liver, spleen, kidneys, adrenals, stomach, pancreas, small intestine,
    large intestine and any unusual lesion of five males and five females,
    high level and control groups.  Weaning survival index, and
    body-weight at weaning was considerably reduced in the 5000 ppm group
    of the F1A and F1B generation.  Reduction of indices was still
    apparent in the F2A and F2B generations, when the dietary level was
    reduced to 2500 ppm.  At the 1000 ppm, the indices were similar to
    control. Redistribution of F2B pups to females of control groups,
    resulted in similar growth of all pups to weaning.  Allowing pups from
    high level group to be nursed by control dams resulted in a marked
    increase in survival indices, whereas when control pups were nursed by
    high level dams, there was a marked decrease in survival indices. 
    Examination of P2 parents following third breeding indicated a
    dose-dependent reduction in implantation sites, as well as a reduction
    in number of corpora lutea.  Fertility index of high level P2 females
    was depressed at the F2C stage.  Skeletal evaluation of F2C litters
    showed incomplete skull ossification in some pups in the test groups,
    but this was not considered remarkable for the size of the foetuses. 

    Necropsy of the pups indicated a higher incidence of gross kidney
    alterations than that observed in controls.  No compound-related
    histology was reported. (Hazleton Lab. Inc. 1970).

    Special studies

    Dermatological effects

    Gallates have been shown to cause contact dermatitis in bakers and
    other workers handling gallates.  Patch tests with lauryl gallate at
    0.2% showed a weak positive response in one sensitized individual.
    Other individuals have suffered recurring episodes of dermatitis
    presumably caused by gallates in food products (Brun, 1970).

    Repeated insult patch test with 0.1% n-octyl gallate solution showed
    an overall incidence of reaction in 13/445 or 2.9% individuals
    (Industrial Biotest Lab., 1971).  Oral mucosa irritation/sensitization
    tests were conducted with beer containing 20 ppm n-octyl gallate and
    showed that the incidence and severity of erythema were greater with
    beer containing n-octyl gallate, than with untreated beer.  Oedema was
    also greater with treated beer.  Individuals that had previously shown
    reactions indicative of sensitization in the patch test were more
    susceptible to irritation (incidence and severity) than other
    individuals (Industrial Biotest Lab., 1971).


    Reproduction studies in the rat show that the mortality of suckled
    young observed at the highest levels were due to a perinatal effect,
    and must have been caused by a factor entering the mother's milk.  It
    has not been established if the reported decrease in implantation
    sites and number of corpora lutea, that occurred at the third breeding
    of the P2 parents is due to an effect on viability of ova or sperm.
    The "no-effect" level in rats, based on reproduction studies is 1000
    ppm (0.1%) of the diet, i.e. 100 mg/kg body-weight/day.

    n-Octyl gallate can cause reactions indicative of sensitization in the
    buccal mucosa of individuals previously sensitized by cutaneous
    contact with the gallate ester.  Because of this observation the use
    of n-octyl gallate in beer or other beverages consumed in large
    amounts is not acceptable.

    Those occupationally exposed to gallate esters should be made aware of
    the sensitizing potential of these substances.


    Brun, R. (1970) Dermatologica, 140, 390

    Hazleton Lab. Inc. (1969a) Unpublished report. Project No. 458-117

    Hazleton Lab. Inc. (1969b) Unpublished report. Project No. 458-115

    Hazleton Lab. Inc. (1970) Unpublished report. Project No. 458-116

    Industrial Biotest Lab. (1970) Unpublished report. IBT No. C8472

    Industrial Biotest Lab. (1971) Unpublished reports. IBT No. P8473;
    IBT No. 8473; IBT No. F9655

    See Also:
       Toxicological Abbreviations