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    WHO/Food Add./24.65
    FAO Nutrition Meetings
    Report Series No. 38A




    SPECIFICATIONS FOR IDENTITY AND 
    PURITY AND TOXICOLOGICAL EVALUATION 
    OF SOME ANTIMICROBIALS AND 
    ANTIOXIDANTS





    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met 8-17
    December 1964a





                   

    a Eighth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1965, 309; FAO
    Nutrition Meetings Report Series 1965, 38.


    DILAURYL THIODIPROPIONATE

    CHEMICAL NAMES        Dilauryl ester of ß,ß'-thiodipropionic acid;
                          dilauryl ester of 3,3'-thiodipropionic acid

    EMPIRICAL FORMULA     C30H58O4S

    STRUCTURAL FORMULA

                          CH2 - CH2 - COO - (CH2)11 - CH3
                          '
                          S
                          '
                          CH2 - CH2 - COO - (CH2)11 - CH3


    MOLECULAR WEIGHT      514.86

    DEFINITION            Dilauryl thiodipropionate is an ester of
                          thiodipropionic acid and a food grade lauryl
                          alcohol.  It contains not less than 99% of
                          C30H58O4S and conforms to the following
                          specifications.

    DESCRIPTION           White crystalline flakes having a
                          characteristic sweetish ester-like odour.

    USE                   As an antioxidant for fats and other
                          foodstuffs.

    IDENTIFICATION

    A.  Solubility:  Water:            Insoluble
                     Organic solvent:  Soluble in most organic solvents

    B.  Solidification point: Not below 40°

    C.  Saponification number: Not less than 210

    PURITY TESTS

    Acidity (as thiodipropionic acid):  Not more than 0.2% of C6H10O4S.

    To 50 ml of a mixture of 1 part of methanol and 3 parts benzene add
    phenolphthalein TS and neutralize with ethanolic potassium hydroxide.
    Add 2 g, accurately weighed, of dilauryl dithiopropionate, swirl to
    dissolve, add 3 drops of phenolphthalein TS and titrate with 0.1 N
    ethanolic potassium hydroxide.  Each ml of 0.1 N ethanolic potassium
    hydroxide is equivalent to 8.91 mg of C6H10O4S.

    Heavy metals:  Not more than 20 mg/kg.

    Place 2 g, accurately weighed, in a porcelain crucible, add sufficient
    nitric acid to wet the sample and ignite carefully at a low
    temperature until thoroughly charred, covering the crucible loosely
    with a porcelain lid during the ignition.  When carbonization is
    complete, add 2 ml of nitric acid and 5 drops of sulfuric acid, heat
    cautiously until white fumes are evolved, and then ignite, preferably
    in a muffle furnace at 550° ± 50° until the carbon is removed.  Cool,
    add 1 ml of diluted hydrochloric acid (1 in 2), cover, and digest on a
    steam bath for 15 minutes.  Remove the cover and evaporate on a steam
    bath to dryness.  Moisten the residue with 0.05 ml of hydrochloric
    acid, add 10 ml of hot water, and digest on a steam bath for 5
    minutes.  Filter if necessary and dilute to 25 ml.

    Arsenic:  Not more than 3 mg/kg.

    Lead:  Not more than 10 mg/kg.

    ASSAY

    Weigh 0.700 g of dilauryl thiodipropionate and add 10 ml of acetic
    acid and 50 ml of ethanol, and heat the mixture gently until the
    sample dissolves completely.  Add 3 ml of hydrochloric acid and 4
    drops of p-ethoxychrysoidin TS and immediately titrate with 0.1 N
    bromide-bromate TS.  As the endpoint is approached (pink colour), add
    4 more drops of the indicator solution and continue the titration,
    dropwise, to a colour change from red to pale yellow.  Perform a blank
    determination and make any necessary correction.  Each ml of 0.1 N 
    bromide-bromate TS is equivalent to 0.02574 g of C30H58O4S. 
    Subtract the per cent. of thiodipropionic acid determined in the
    acidity tests from the per cent. of dilauryl thiodipropionate
    calculated from this titration to obtain the per cent. of C30H58O4S.

    Biological Data

    Biochemical aspects

    No information available.

    Acute Toxicity

                                                                                          

                         Animal      Route                   LD50          Reference
                                                           (mg/kg 
                                                          body-weight)
                                                                                      

    Thiodipropionic      Mouse       oral                    2000              1
    acid                 Mouse       intraperitoneal          250              1
                         Mouse       intravenous              175              1

                         Rat         oral                    3000              1
                         Rat         intraperitoneal          500              1
                         Rat         intravenous             >300              1

    Dilauryl             Mouse       oral                   >2000              1
    thiodipropionate     Mouse       intraparitoneal        >2000              1

                         Rat         oral                   >2500              1

    Distearyl            Mouse       oral                   >2000              1
    thiodipropionate     Mouse       intraperitoneal        >2000              1

                         Rat         oral                   >2500              1
                                                                                      
    
    Short-term studies

    Rat.  Mixtures of thiodipropionic acid and dilauryl thiodipropionate
    were heated with lard in concentrations at least 10 times that
    recommended for use and fed to rats.  There was no detectable toxic
    effect.1

    Guinea-pig.  Thiodipropionic acid was fed to guinea-pigs at a level
    of 0.5% in the drinking-water for a period of 120 days.  No
    significant effect was noted on weight or mortality.1

    Dog.  Dogs were fed a mixture of 10 parts by weight of dilauryl
    thiodipropionate and 1 part of thiodipropionic acid in the diet at
    concentrations of 0.1% and 3.0% of the acid-ester mixture.  No
    untoward effects were noted over a period of 100 days.

    Long-term studies

    Rat.  Thiodipropionic acid or its dilauryl or distearyl ester was
    fed to groups of 20 rats each at levels of 0%, 0.5%, 1.0% and 3.0% in
    the diet for a period of 2 years.  No discernable adverse effects were
    observed in any of the experimental animals, as determined by growth
    rate, mortality, and pathological examination.1

    Comment on experimental studies reported

    It would be desirable to have further details on the experimental work
    that has been carried out on thiodipropionic acid; the published
    report gives only a summary.  Biochemical studies and observations on
    human subjects are not available.

    Evaluation

    Level causing no significant toxicological effect in the rat

    3.0% (= 30 000 ppm) in the diet, equivalent to 1500 mg/kg body-weight
    per day.

    Estimate of acceptable daily intakes for man

                                         mg/kg body-weight

             Unconditional acceptance           0-3.0
             Conditional acceptance            3.0-15.0

    Further Work Considered Desirable

    1.  Long-term studies in a species other than the rat.

    2. Biochemical studies in animals and in man.

    Reference

    1.  Lehman, A. J., Fitzhugh, O. G., Nelson, A. A. & Woodard, G. (1951)
    Advanc. Food Res., 3, 197
    



    See Also:
       Toxicological Abbreviations
       DILAURYL THIODIPROPIONATE (JECFA Evaluation)