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    FAO Nutrition Meetings
    Report Series No. 40A,B,C
    WHO/Food Add./67.29




    TOXICOLOGICAL EVALUATION OF SOME
    ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
    STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES





    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
    13-20 December, 19651 Geneva, 11-18 October, 19662




                   

    1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1966 No. 40; 
    Wld Hlth Org. techn. Rep. Ser., 1966, 339

    2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series, 1967, in press; 


    Food and Agriculture Organization of the United Nations
    World Health Organization
    1967


    STEARYL TARTRATE

    Synonym                       Stearyl palmityl tartrate

    Chemical description          Di-stearyl/palmityl tartrate

    Empirical formula             C40H78O6 to C38H74O6

    Structural formula            HO-CH-COOR
                                     '
                                  HO-CH-COOR

                                  Where R = (CH2)17-CH3 or up to 50 per
                                  cent. (CH2)15-CH3

    Molecular weight              654 to 626

    Definition                    The material shall be the product of the
                                  esterification of tartaric acid with
                                  commercial stearyl alcohol, which
                                  consists essentially of stearyl and
                                  palmityl alcohols.

                                  It shall consist mainly of di-ester,
                                  with minor amounts of mono-ester and of
                                  unchanged starting materials, the total
                                  ester content being not less than 90 per
                                  cent. by weight.

    Description                   Stearyl tartrate occurs as a
                                  cream-coloured unctuous substance.

    Use                           As a dough strengthening agent.

    Biological Data

    Biochemical aspects

         Stearyl tartrate is made from stearyl alcohol and tartaric acid.
    The only impurities present in any significant amount are unreacted
    stearyl alcohol and tartaric acid. Both of these substances occur
    naturally in the diet and they have no toxicological significance at
    the level of use of stearyl tartrate. Commercial stearyl alcohol
    contains 50 per cent. cetyl alcohol which is handled similarly to
    stearyl alcohol in the body. The use of deuterium-labelled cetyl and
    stearyl alcohol has shown that they are largely converted into the
    corresponding palmitic and stearic acids which mix with fatty acid
    pool and enter normal metabolism. The actual proportion of cetyl and
    stearyl alcohol is not expected to make any difference in their
    biological effect (Den Stetten & Schoenheimer, 1940; Schoenheimer &
    Hilgetag, 1934). The ester linkage between the primary alcohol and

    tartaric acid is split by liver esterases but not by pancreatic
    lipase. 14C-labelled stearyl tartrate was poorly absorbed in rats
    when fed as a suspension in water, or mixed with food; about 90 per
    cent. or more was recovered from the stools. When labelled stearyl
    tartrate was administered as a 1 per cent. solution in olive oil,
    50-80 per cent. was absorbed in 7 out of 10 rats; the other 3 rats
    showed poor absorption. Study of the metabolism of labelled stearyl
    tartrate, administered as an oily solution was carried out in rats
    using a closed system for the recovery of 14CO2. It was shown that
    carbon dioxide was released from stearyl tartrate at a rate equivalent
    to the elimination of 13.5 mg of stearyl tartrate/kg body-weight/24 h.
    Continued administration of stearyl tartrate over a period of 10 days
    did not cause any reduction in its rate of metabolism. There was no
    preferential accumulation of labelled stearyl tartrate in any organs
    or in adipose tissue over the period of these experiments. The rate of
    elimination demonstrated exceeded the rate of absorption, so that
    cumulation would not be expected to occur (Frazer et al., 1954a;
    Frazer, 1955).

         The absorption of olive oil containing 1 per cent. of stearyl
    tartrate over a period of 3 hours in the rat was compared with the
    absorption of olive oil alone in groups of 10 rats. The average
    absorption in the two groups was 83 per cent. and 86 per cent.
    respectively after administration of 1.0 ml of oil intragastrically.
    The gross and microscopic appearances of the small intestine were
    normal in all animals (Frazer et al., 1954b).

    Acute toxicity

         Single doses of up to 5000 mg/kg orally and up to 2000 mg/kg.i.m.
    of stearyl tartrate in aqueous or oily vehicle were administered to
    groups of mice, rats, guinea-pigs, rabbits and dogs. Over the dosage
    range studied, no abnormalities were detected that could be attributed
    to the administration of stearyl tartrate (Frazer et al., 1954b).

    Short-term studies

         Rat. Groups of 50 male weanling rats were fed diets containing
    0, 2.5 and 5 per cent. of stearyl tartrate. Appearance, behaviour and
    rate of weight gain in the three groups showed no significant
    difference during the rapid growth period. At 15 months no significant
    differences were found in hepatic and renal function between control
    and treated groups. Gross and histopathological examinations of the
    main organs on autopsy revealed no abnormalities attributable to
    stearyl tartrate (Ahmad, 1953; Frazer et al., 1954b).

         Man. Bread was fed to 15 human volunteers for a period of 4
    years. Ten received bread containing 0.075 per cent. of stearyl
    tartrate and 5 received untreated bread. No difference was observed
    between the groups with regard to general health, appetite,
    body-weight, haemoglobin, blood counts and urinary constituents
    (Frazer et al., 1954b).

    Long-term studies

         Mouse. Four groups of male and female mice were fed diets
    containing either 57 per cent. of untreated bread, or 57 per cent. of
    bread treated with 3.2 per cent. of stearyl tartrate, or diets
    containing 3.2 per cent. of glyceryl monostearate or 3.2 per cent. of
    stearyl tartrate plus 3.2 per cent. of glyceryl monostearate. Nine
    generations of mice were studied. At the start of the experiment one
    of the stearyl tartrate groups developed an infection and the group
    had to be restocked; however a further 9 generations were produced on
    this diet without any difficulties. No significant difference was
    observed between the groups, in regard to reproduction, lactation,
    weight gain of the young, general health, appearance and survival
    (Frazer et al., 1954b).

         Rat. Four groups of 10 male and 10 female rats were fed diets
    containing 57 per cent. of bread either untreated or treated with 3.2
    per cent. of stearyl tartrate, 3.2 per cent. of glyceryl monostearate
    or 3.2 per cent. of stearyl tartrate plus 3.2 per cent. of glyceryl
    monostearate. These diets were fed for the life span. The appearance,
    behaviour, rate of weight gain, and general health of these animals
    was kept under close observation. At the end of the period the
    survivors were killed and autopsied. The main organs were examined
    microscopically. There were no apparent differences in tumour
    incidence, nor other pathological changes (Frazer et al., 1954b).

         Four groups of male and female rats were fed the diets described
    above. Four generations of rats were studied. No significant
    difference was observed between the different groups in regard to
    reproduction, lactation, rate of weight gain of young, general
    appearance and survival (Frazer et al., 1954b).

         Groups of 10 male and 40 female rats were fed a control diet and
    diets containing bread treated with 1 or 5 per cent. stearyl tartrate.
    The second and third generations of animals on these diets were
    followed for their life span. At 36 weeks, there was no significant
    difference in body-weight gain. Hepatic function, reproduction and
    lactation, and morbidity or mortality showed no significant difference
    between the three groups. When killed at the end of two years no
    statistically significant difference was found between the control and
    the test groups with regard to pathological findings or tumour
    incidence (Frazer et al., 1954 b).

    Comments

         Stearyl tartrate has been extensively studied in animals.
    Metabolic studies in the rat revealed that it is poorly absorbed under
    ordinary circumstance, but that if it is absorbed it can be
    metabolized and does not accumulate in the tissues. There exists
    little doubt concerning the safety and freedom from carcinogenic
    hazard of stearyl tartrate.

    Evaluation

    Acceptable level of treatment

                        Bread: 0-500 mg/kg flour.

    REFERENCES

    Ahmad, N. U. (1953) Toxicological studies of fatty acid esters and
    related compounds, Ph.D. thesis, University of Birmingham, summary
    submitted to WHO

    Frazer, A. C. (1955) Voeding 16, 535

    Frazer, A. C., Pover, W. F. R. & Simmons, H. G. (1954a) Proc. Second
    Radio-isotope Conference, I, 298, Butterworth, London

    Frazer, A. C., Ahmad, N. U., Hickman, J. R., Sharratt, M., Pover, W.
    W. F. R. & Sammons, H. G. (1954b) Unpublished report submitted to WHO
    


    See Also:
       Toxicological Abbreviations
       STEARYL TARTRATE (JECFA Evaluation)