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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, EMULSIFIERS, STABILIZERS,
    ANTI-CAKING AGENTS AND CERTAIN
    OTHER SUBSTANCES



    FAO Nutrition Meetings Report Series 
    No. 46A WHO/FOOD ADD/70.36




    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    27 May - 4 June 19691





    Food and Agriculture Organization of the United Nations

    World Health Organization



                   
    1 Thirteenth 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.


    OXYSTREARIN

    Biological Data

    Biochemical aspects

    Analyses of diets and feces of rats maintained for one month in diets
    containing five to 15 per cent. oxystearin, showed that 70 per cent.
    of the ingested oxystearin was absorbed. Liver lipids remained normal,
    but carcass lipids showed decreasing iodine values, with increasing
    dietary oxystearin (Mattson, 1951). In another experiment, utilization
    of the ether soluble material at three and 15 months in rats
    maintained on a 15 per cent. oxystearin diet was 61-83 per cent.
    (Hodge, 1954)

    Acute toxicity

    Rat. per os, intraperitoneally, LD50 have not been established.
    Female rats were able to tolerate doses as high as 15 g/kg without any
    marked ill-effects. (Hodge, 1952)

    Short-term studies

    Rat. Groups each of 20 rats (10 of each sex) were maintained for 30
    days on diets containing 0, 0.5, 2.0 and 20 per cent, oxystearin. No
    deaths occurred. Retarded growth rates were reported at the 20 per
    cent. level. Organ weights were normal. (Hodge, 1952)

    In another study, groups of 20 rats (10 of each sex) were maintained
    on diets containing 0, 0.15, 5, 10 and 15 per cent. oxystearin for one
    month. There was no effect on weight gain or haematological indices of
    blood. The weights of all organs were normal (Hodge, 1952).

    Dogs. A single female dog tolerated a diet containing 25 per cent.
    oxystearin for one month. Haematologic indices of blood were normal as
    were urine sugar and protein. At autopsy, organ weights were within
    normal limits and there were no compound related histological changes
    (Hodge, 1952).

    Groups each of four dogs (two of each sex) were fed diets containing
    0, 0.25 and 2.5 per cent. oxystearin for one year. Observations
    included general condition, growth rate, food intake, urine analyses,
    hematological indices of blood, organ weight and histopathology. All
    findings were negative. (Hodge, 1954)

    Long-term studies

    Mouse. 300 mg per week of oxystearin was administered to the skin of
    38 mice in three doses for 75 weeks. The tumour index (per cent  -
    weeks) was negative for a cottonseed oil control, a 40 per cent.
    solution of oxystearin in cottonseed oil, and a 40 per cent.

    unsaponifiable fraction of oxystearin in cottonseed oil. The positive
    control methylcholanthrene had a tumour index of 89 per cent. - 69
    (Horton, 1956).

    Rats. Groups each of 100 rats (50 of each sex) were fed a diet
    containing 0, 0.5, 5.0 and 15.0 per cent. oxystearin for two years.
    There was no indication that oxystearin shortened the life span.
    Growth rate and food consumption was normal, with the exception of the
    15 per cent. group, where there was a slight retardation in growth
    during the first 90 days, but this difference had disappeared by the
    end of the first year. Urine analyses gave normal values for sugar
    protein. Haematological indices of blood were normal, with the
    exception of females at the 15 per cent. level, where there was a
    slight depression in haemoglobin and red blood cell counts. At
    autopsy, organ weights were normal with the exception of liver weight,
    at the 5 per cent. and 15 per cent. level. No histological changes
    occurred in the liver or other organs and tissues examined that could
    be related to the test substances. A study of femur length and
    radiographs of these bones showed no effect on bone structure (Hodge,
    1954).

    A three generation reproduction study in rats selected from the 0, 0.5
    and 5 per cent. groups (16 females and 8 males), showed that there
    were no effects on reproductive performance as measured by number of
    pregnancies, rats born, pups per litter, mortality 0-5 days, 6-12
    days; and average weight at end of 21 days. Organ weights of the F3b
    generation were within normal range; although organ/ body weight
    ratios of test groups were greater than control, because of slightly
    lower body-weight of these groups (Hodge, 1954).

    Comments

    Metabolic studies indicate that the fatty acids are absorbed and
    utilized and there are adequate short-term and long-term studies
    available for assessment. There is no evidence of accumulation of the
    saturated fatty acids in the liver cells, although compositional
    changes in body fat are reported. Provision is made in the
    specification for limitation of epoxide content.

    EVALUATION

    Level causing no significant toxicological effect in the rat

    Five per cent. (= 50 000 ppm) in the diet equivalent to 2500 mg/kg
    body-weight/day

    Estimate of acceptable daily intakes for man

                                            mg/kg body-weight

    Unconditional acceptance                       0 - 25

    REFERENCES

    Hodge, H. (1952) Unpublished report, Proctor & Gamble Co.

    Hodge, H. (1954) Unpublished report, Procter & Gamble Co.

    Horton, A. W, (1956) Unpublished report, Proctor & Gamble Co.

    Mattson, F. H. (1951) cited in Hodge, H. (1952) Unpublished report
    submitted by Procter & Gamble Co.
    


    See Also:
       Toxicological Abbreviations
       Oxystearin (WHO Food Additives Series 5)
       OXYSTEARIN (JECFA Evaluation)