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


    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


    Chemical names               Propylene glycol ether of

    Chemical formula

            [C6H7O2(OH)z(OCH3) x (OCH2CHOHCH3)y]n

            where x : 1.12-2.03 )
                  y : 0.07-0.34 ) : degrees of substitution
                  z : 3-(x+y)

    Structural formula


    Molecular weight             Unsubstituted structural unit: 162.14

                                 Structural unit with 1.19 degree of
                                 substitution: approx. 180

                                 Structural unit with 2.37 degree of
                                 substitution: approx. 210

                                 Low polymers (n about 70): approx.
                                 13 000

                                 High polymers (n about 1000): approx.
                                 208 000

    Definition                   Hydroxypropyl methylcellulose is a
                                 methylcellulose modified with a small
                                 amount of propylene glycol ether groups
                                 attached to the anhydroglucose of the
                                 cellulose. The dry product contains 19
                                 per cent. to 30 per cent. of methoxyl
                                 (-OCH3) groups and 3 per cent. to 12
                                 per cent. of hydroxypropyl
                                 (-OCH2CHOHCH3) groups.

    Description                  Hydroxylpropyl methylcellulose is a
                                 white fibrous powder or as granules

    Uses                         As a thickening agent or stabilizer.

    Biological Data

    Biochemical aspects

         Twenty-five young human adults ingested doses ranging from 0.6 to
    8.9 g of type B on three separate occasions. Only a mild laxative or
    constipating effect was noted in several cases. About 97 per cent. of
    the dose, determined as methoxy groups, was recovered from faeces
    (Knight et al., 1952).

    Acute toxicity of type B


    Animal      Route        LD50               References

    Mouse       i.p.         5 000              Hodge et al., 1950

    Rat         i.p.         5 000              Hodge et al., 1950

    Short-term studies

         Rat. Groups of 10 male and 10 female weanling rats were fed
    diets containing 0, 2, 10 and 25 per cent. type B for 30 days. Only in
    the highest dose were interference with body-weight gain and diarrhoea
    observed. There no histological lesions nor were there abnormal
    findings in urine and blood (Hodge et al., 1950).

         Groups of 10 and 10 female young rats were fed 0, 1, 3, 10 and 30
    per cent. of type A for 121 days. Body-weight gain was markedly
    retarded at the 30 per cent. level, with 50 per cent. mortality
    attributed to under-nutrition. Only the male rats showed slight
    body-weight gain retardation at the 10 per cent. dietary level, while
    the weight-gain was normal at the lower levels. Histological
    examination of internal organs revealed no abnormalities in any of the
    5 groups (McCollister & Oyen, 1954).

         Groups of 10 male and 10 female young rats were fed diets
    containing 0, 0.3, 1, 10 and 20 per cent. of type C. for 90 days. At
    the 20 per cent. level both sexes showed marked retardation of
    body-weight gain, with 30 per cent. mortality. At the 10 per cent.
    level male rats only showed slight but significant weight gain

    retardation. At the lower levels there were no adverse effects. The
    microscopic appearance of tissues was normal at all levels
    (McCollister et al., 1961).

         Groups of 10 male and 10 female young rats were fed 0, 0.3, 1, 3,
    10 and 20 per cent. of type D for 84 days. No adverse effects were
    noted with female rats at all levels. Male rats showed a definite
    retardation of bodyweight gain at 20 per cent. level and a slight
    retardation at 10 per cent. Organ weights and gross and microscopic
    examination revealed no adverse effects (McCollister et al., 1961).

         Rabbit. Groups of 6 rabbits were fed diets containing 0, 10 and
    25 per cent. type B for 30 days. The group on the highest dose
    maintained, but did not increase, their body-weight. Normal results
    were obtained from urine and blood analyses, comparison of organ
    weights and histological examination (Hodge et al., 1950).

         Dog. Groups of 2 dogs were fed for one year 0.1, 0.3, 1.0 and
    3.0 g/kg body-weight daily of type B without effect on body and organ
    weights, urine, blood and microscopic appearance of internal organs.
    One dog fed 25 g/kg body-weight daily for 30 days suffered no ill
    effects. Another dog fed 50 g/kg body-weight daily for 30 days
    exhibited some diarrhoea, slight weight loss and slight depression of
    red blood cell count without any histological changes (Hodge et al.,

    Long-term studies

         Rat. Groups of 50 male and 50 female rats were fed for 2 years
    on diets containing 0, 1, 5 and 20 per cent. of type B. There was a
    slight retardation of body-weight gain in the male group at the
    highest dose. Mortality ranged from 60-84 per cent. with no
    significant difference between the groups. Tumour incidence was the
    same in the experimental groups as in controls (Hodge et al., 1950).


         No significant amounts appear to be absorbed from the digestive
    tract in man. There are no acute oral toxicity data, and only one
    long-term study has been done on one particular type. Short-term
    studies have been done with four slightly different, types, but gave
    consistent results.


    Level causing no toxicological effect

         Rat. 50 000 ppm in the diet, equivalent to 2500 mg/kg

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

       Unconditional acceptance             0-301

       Conditional acceptance :        Higher levels may be used for
                                       dietetic or calorie control


    Hodge, H. C., Maynard, E. A., Wilt, W. G. jr, Blanchett, H. J. jr &
    Hyatt, R. E. (1950) J. Pharmacol. exp. Ther., 99, 112

    Knight, H. F., Hodge, H. C., Samsel, E. P., Delap, R. E. &
    McCollister, D. D. (1952) J. Amer. pharm. Ass., sci. Ed., 41, 427

    McCollister, D. D. & Oyen, F. (1954) J. Amer, pharm. Ass., sci.
    Ed.,, 43, 664

    McCollister, D. D., Oyen, F. & Greminger, G. K. jr (1961) J. Pharm.
    Sci., 50, 615


    1 As sum of total cellulose derivatives.


    See Also:
       Toxicological Abbreviations