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                      Ethyl p-oxybenzoate; Ethylparaben

    Chemical name                 Ethyl p-hydroxybenzoate; ethyl ester of
                                  p-hydroxybenzoic acid

    Empirical formula             C9H10O3

    Structural formula


    Molecular weight              166.18

    Definition                    Ethyl p-hydroxybenzoate, after drying
                                  for 2 hours at 80°, contains not less
                                  than 99 per cent. of C9H10O3.

    Description                   Ethyl 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 its 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 metabolism of the ethyl ester is similar to that of the
    methyl ester. Dogs given 1000 mg/kg body-weight orally or 50 mg/kg
    i.v. excreted 66-70 per cent. in the urine. Very low plasma levels,
    just detectable, were found two hours after oral administration or at
    5 and 15 minutes after i.v. injection (Sokol, 1952).

         Human studies on six subjects involved administration of 10 or 20
    mg/kg body-weight of ester orally. After 60, 135 and 255 minutes,
    n-hydroxybenzoate but not the ester, was detectable in serum. The
    maximum serum level attained was 4.5 µg/ml (Heim, 1960-1).

    Acute Toxicity


    Animal         Route     LD 50            References

    Mouse          oral      8 000            Sokol, 1952

    Guinea-pig     oral      2 000-2 400      Heyden, 1939

    Rabbit         oral      5 000            Sabalitschka & Neufeld-
                                              Crzellitzer, 1954

    Dog            oral      5 000            Sabalitschka &
                                              Neufeld-Crzellitzer, 1954

    Short-term studies

         Rabbit. Suspensions of 0.5 and 7.5 per cent. ethyl
    p-hydroxybenzoate had the same local anaesthetic effect on the cornea
    as 0.12 and 0.27 per cent. solutions of cocaine hydrochloride.
    Therefore, the local anaesthetic activity of the ester is 3-4 times
    less than that of cocaine and twice that of procaine (Truhaut, 1962).
    Using the same method of Regnier & Quevauviller (1939), Adler-Hradecky
    and Kelentey (1960) found no local anaesthetic effect on the cornea by
    0.25-0.30 per cent. solutions of methyl, ethyl, propyl or butyl

    Long-term studies

         Rat. Forty rats were fed 15 mg/kg body-weight, 20 animals 150
    mg/kg body-weight and 20 animals 1500 mg/kg body-weight of a mixture
    of 40 per cent. ethyl ester and 60 per cent. propyl ester as the
    sodium salts for 18 months in the diet. The rate of weight gain showed
    some growth stimulation at the 15 and 150 mg/kg body-weight levels.
    The group on 1500 mg/kg body-weight showed initial retardation
    followed later by normal growth. Mortality rate and pathological
    examination of the major organs in all treated groups showed no
    significant difference from the control group (Heyden, 1940; Heyden,

         A group of 65 rats (35 males and 30 females) was fed a diet
    containing 2 per cent. of the ethyl ester for the life span, with 50
    animals as the control group. All animals were autopsied on death. No
    adverse effects could be detected on weight gain, except a small
    retardation during the first month, and the mortality rate,
    haematology, tumour incidence and histopathology of major organs did
    not differ from the controls (Truhaut, 1962).

         A group of 39 rats (19 males and 20 females) was injected weekly
    with 1 ml of an aqueous solution of 10 per cent. sodium ethyl
    p-hydroxybenzoate for their life span. The 27 controls (16 males and
    11 females) were injected with 1 ml of a 3 per cent. sodium chloride
    solution. Because of irritation by the high p.H of the ester solution,
    the frequency of injection had to be reduced to 1 in 2 weeks from the
    4th to the 10th month and later to 1 injection a month up to the end
    of the experiment. No effect on mortality and tumour incidence could
    be detected (Truhaut, 1962).


         The long-term studies in rats are adequate for assessment, taking
    into consideration the data on methyl and propyl p-hydroxybenzoates.
    However, further biochemical studies in man and animals are desirable
    and further studies on the local anaesthetic action should also be


    (See propyl p-hydroxybenzoate)


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

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

    Heim, F. (1960-1) Sitzber. Physik-Med. Soz. Erlangen, 81, 14

    Heyden,-. (1939) Unpublished Report from Applied Research Inc., MX-124

    Heyden, -. (1940) Unpublished Report from Applied Research Inc.,

    Heyden, -. (1942) Unpublished Report from Applied Research Inc.,

    Regnier, M. & Quevauviller, A. (1939) Arch. exp. Path. Pharm.,
    193, 48

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

    Schübel, K. & Manger, J. (1929) Arch. exp. Path. Pharmak., 146,

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

    Truhaut, R. (1962) Estratto dai Rendiconti dell'Instituto Superiore di
    Sanità (Document submitted to WHO in 1964)

    See Also:
       Toxicological Abbreviations