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.


    Biological Data 

    Biochemical aspects

    Wesley et al. (1965) identified propylene chlorohydrin as the residue
    formed in foods fumigated with propylene oxide. The chlorohydrin is
    formed by the reaction of the epoxide with the chloride of food.
    Previously, it had been believed that propylene glycol, formed by
    reaction with water in the food, was the residue. Propylene
    chlorohydrin is also formed in starches modified by
    hydroxypropylation. Both propylene chlorohydrin isomers have been
    identified in fumigated foods (Ragelis et al. 1966).

    When volatilization was precluded, a combination of high temperature
    and prolonged time in cooking did not appreciably alter the propylene
    chlorohydrin content of food, but when volatilization was possible,
    the chlorohydrin content was reduced 50 per cent. by cooking (Wesley
    et al. 1965). When propylene chlorohydrin was added to a standard
    ground laboratory rat diet, 20 minutes of mixing in an open mixer at
    room temperature resulted in a 65 per cent. decrease in the propylene
    chlorohydrin content (USFDA, 1966).

    Acute toxicity


    Animal    Route             LD50                  Reference
                        (mg/kg body weight)

    Rat       oral               218                  USFDA, 1969

    Dog       oral      150 mg/kg - no deaths         USFDA, 1969
                        200 mg/kg - 1/7 deaths
                        250, 300 mg/kg - 6/6 deaths

    Short-term toxicity

    Rat. Groups of 10 male and 10 female five-week-old rats were fed,
    for 25 weeks, diets to which propylene chlorohydrin had been added.

    The planned dietary levels were 0, 1000, 2500, 5000, and 10 000 ppm,
    but analysis of the 10 000 ppm diet after mixing in the test compound
    (open mixer, 20 minute mixing time, room temperature) showed an actual
    concentration of 3568 ppm or 35 per cent. of the planned level. The
    2-chloro isomer constituted 27 per cent. of the total found. The
    actual level in this diet, after seven days exposure to laboratory
    conditions, was reduced to 838 ppm, with 32 per cent. of the 2-chloro
    isomer, or less than 10 per cent. of the planned concentration.

    Weight gain in both sexes on the 5000 and 10 000 ppm levels was
    depressed. The depression was slight in the males on the 5000 ppm
    level and both groups of females and moderate in the males on the 10
    000 ppm level. Food consumption was slightly decreased in these groups
    but food efficiency was normal. The average liver, and kidney weights
    of the males and the liver weight of the females on the 10 000 ppm
    level were decreased but the organ weight/body weight ratios were
    normal. The decreased spleen weights and spleen/body weight ratios
    in the males and other minor organ weight variations appeared to be
    unrelated to the treatment. No effects on haematological values,
    mortality, or gross or microscopic lesions in the tissues were
    observed (USFDA, 1969).

    Propylene chlorohydrin was administered to groups of 10 male and 10
    female eight-week old rats by stomach tube in doses of 0, 25, 50, 75,
    and 100 mg/kg/day for 22 weeks. The dose for the high level was
    increased from 100 mg/kg to 150 mg/kg in the eleventh week, to 200
    mg/kg in the fourteenth week, and to 250 mg/kg in the sixteenth week.
    Doses of 200 mg/kg and less did not increase mortality. All the rate
    on the high level were dead by the nineteenth week with all but one of
    the deaths occurring between the sixteenth and nineteenth weeks after
    the dose had been increased to 250 mg/kg. On the high level, weight
    gain was moderately depressed in the males and slightly depressed in
    the females while the dose was 100 or 150 mg/kg. Both sexes lost
    weight when the dose was increased to 200 mg/kg. Weight gain was
    slightly, but not significantly, decreased in both sexes on the 75
    mg/kg level. Food consumption was slightly decreased in the males of
    the high level while the dose was 100 mg/kg and decreased to a greater
    extent when the dose was raised. The females on the high level also
    showed a slight decrease in food consumption when the dose was
    increased. With the rats losing weight when the dose was increased to
    200 mg/kg, the food efficiency values have no meaning. The liver
    weight/body weight ratios of both males and females on the 75 mg/kg
    dose and the liver weight and liver weight/body weight ratio of the
    males on the 25 mg/kg dose were increased, but this increase was not
    accompanied by gross or microscopic alterations in the liver. Other
    organ weight and organ weight/body weight ratio changes did not appear
    to be related to the treatment. No haematological effects or gross or
    microscopic effects on the tissues of the treated rats, at a dose of
    75 mg/kg or less, were seen. The tissues of the high level rats were
    not examined microscopically (USFDA, 1969).


    Although in vitro enzymatic digestion tests revealed no
    abnormalities there was some evidence that a high degree of
    substitution rendered the product less digestible at the 25 per cent.
    dietary level. The 90-day tests are adequate and point to 10 per cent.
    in the diet as the no-effect level. Information is desirable on the
    metabolic behaviour preferably in man - of the moiety containing the
    propylene glycol ether.


    Level causing no toxicological effect in the rat

    Ten per cent, (= 100 000 ppm) in the diet equivalent to 5000 mg/kg
    body weight/day.

    Estimate of acceptable daily intake for man

    Temporary acceptance                    mg/kg body weight

                                                 0 - 25

    Further work required by June 1972

    Ninety-day tests in a non-rodent mammalian species using material
    modified to the highest degree employed as food additive.


    Feron, V. J., Til, H. P. & de Groot, A. P. (1967) Unpublished report
    by Centraal Instituut voom Voedings anderzoek TNO, No. R2456

    Kay, J. H. & Calandra, J. C. (1961) Unpublished report by Industrial
    Bio-Test Laboratories, Inc. 17th November 1961

    Kay, J. H. & Calandra, J. C. (1962) Unpublished report by Industrial
    Bio-Test Laboratories, Inc. 22nd January 1962

    Majors, P. A. & Rubenkoenig, H. L. (1959) Unpublished report by Hill
    Top Research Institute, Inc. 18th May 1959

    Pallotta, A. J. (1959) Unpublished report by Hazleton Laboratories,
    Inc. 22nd May 1959

    Ragelis, E. P., Fisher, B. S. & Klimeck, B. A. (1966) J.O.A.C., 49,

    Rubenkoenig, H. L. (1959) Unpublished report by Hill Top Research
    Institute, Inc. 13th May 1959

    United States Food and Drug Administration (1969) Unpublished data

    Wesley, F., Rourke, B. & Darbishire, O. (1965) J. Fd. Sci., 30, 1037

    See Also:
       Toxicological Abbreviations