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


    Synonyms                      Methyl p-oxybenzoate; Methylparaben

    Chemical Name                 Methyl p-hydroxybenzoate; methyl ester
                                  of p-hydrobenzoic acid

    Empirical formula             C8H8O3

    Structural formula


    Molecular weight              152.15

    Definition                    Methyl p-hydroxybenzoate, after dying
                                  for 2 hours at 80, contains not less
                                  than 99 per cent. of C8H8O3 

    Description                   Methyl p-hydroxybenzoate is a white,
                                  almost odourless, crystalline solid.

    Use                           As an antimicrobial agent.

    Biological Data

         This additive was evaluated by the Joint FAO/WHO Expert Committee
    on Food Additives in their Sixth Report (FAO/WHO, 1962). Since its
    publication some new experimental work has been carried out on these
    compounds. This and other work not included in the Sixth Report is
    presented and discussed in this monograph.

    Biochemical aspects

         The alkyl esters of p-hydroxybenzoic acid are well absorbed after
    oral administration to dogs. In dogs the diglucuronide of
    p-hydroxybenzoic acid has been shown to be the main metabolite
    excreted in the urine. Man excreted free p-hydroxybenzoic acid and
    p-hydroxyhippuric acid in approximately equal proportions (Quick,
    1932). The urine of rats receiving p-hydroxybenzoic acid or its

    methyl, ethyl or propyl esters contained the following metabolites:
    p-hydroxybenzoic acid 40 per cent., p-hydroxyhippuric acid 23.5 per
    cent., ether sulfate 5 per cent., ester glucuronides 23 per cent.
    ether glucuronides 1.2 per cent. and 5 per of an unidentified
    substance (Derache & Gourdon, 1963).

         Dogs given 50 mg/kg body-weight intravenously or orally, excreted
    85-89 per cent. in the urine within 48 hours. After intravenous
    injection significant levels were found in the plasma only immediately
    afterwards. When dogs were infused at the rate of 2 mg/kg/minute until
    a total of 100 mg/kg body-weight was given, the levels in most organs
    were below the plasma level. Appreciable amounts were only present in
    liver and kidneys. No accumulation was noted in a dog given 1 mg/kg
    body-weight of the methyl ester orally every day for a period of one
    year. This dog excreted 96 per cent. of the daily dose within 24 hours
    in the urine (Sokol, 1952).

    Special studies

         The blocking effect of a 0.1 per cent. solution of the methyl
    ester on nervous conduction when applied directly to the spinal roots
    or to the cervical vagus and sympathetics was found to be similar to
    that of a 0.05 per cent. solution of procaine (Nathan & Smears, 1961).
    The local anaesthetic effect of the esters rose with increasing number
    of C-atoms and the toxicity decreased (Adler-Hradecky & Kelentey,

    Acute toxicity


    Animal         Route     LD 50            References

    Mouse          oral      8 000            Sokol, 1952
    Guinea-pig     oral      3 000-3 600      Heyden, 1939
    Rabbit         oral      6 000            Sabalitscheka & Neufeld
                                              Crzellitzer, 1954
    Dog            oral      6 000            Sabalitschka & Neufeld
                                              Crzellitzer, 1954

    Short-term studies

         Rat. Groups of 10 animals on a vitamin A deficient diet given
    7.575 mg/kg body-weight of mixed methyl and propyl ester for 30 days
    showed no additional pathological changes (Cremer, 1935).

         Man. Two grams of the ester taken daily for 1 month produced
    no ill effects, (Sabalitschka & Dietrich, 1924).

    Long-term studies

         Rat. When the methyl and propyl esters were fed to rats over
    an 18-month period at a level of 150 mg/kg body-weight, no ill effects
    were observed. There was some evidence of growth stimulation. When fed
    at 1500 mg/kg body-weight, there was a decrease in growth rate, but no
    pathological changes could be found (Sokol, 1952).


         The long-term studies in rats are adequate for an assessment when
    taken in conjunction with the evidence from the feeding experiment
    lasting for a year with dogs. However, further biochemical studies in
    man and animals are desirable and further studies on local anaesthetic
    activity should also be undertaken.


    (See propyl p-hydroxybenzoate)


    Adler-Hradecky, C. & Kelentey, B. (1960) Arch. int, Pharmacodyn.,
    128, 135

    Cremer, H. (1935) Z. Lebensmitt. Untersuch., 70, 136

    Derache, R. & Gourdon, J. (1963) Food Cosmet. Toxicol., 1, 189

    FAO/WHO (1962) FAO Nutrition Meetings Report Series, No. 31;
    Wld Hlth Org. techn. Rep. Ser.,228

    Heyden, (1939) Unpublished report submitted by Applied Research

    Nathan, P. W. & Sears, T. A. (1961) Nature (Lond.), 192, 668

    Quick, A. J. (1932) J. biol. Chem., 97, 403

    Sabalitschka, T. & Dietrich. K. R. (1924) Pharmaz. Monatshefte,
    5, 235

    Sabalitachka, T. & Neufeld-Crzellitzer, R. (1954) Arzneimitt.-
    Forsch, 4, 575

    Sokol, H. (1952) Drug Stand., 20, 89

    See Also:
       Toxicological Abbreviations