WHO/Food Add./24.65
    FAO Nutrition Meetings
    Report Series No. 38A


    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met 8-17
    December 1964a


    a Eighth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1965, 309; FAO
    Nutrition Meetings Report Series 1965, 38.


    CHEMICAL NAMES           Sulfur dioxide; sulfurous acid anhydride


    MOLECULAR WEIGHT         64.1

    DEFINITION               Sulfur dioxide contains not less than 95% SO2

    DESCRIPTION              A colourless, non-inflammable gas with a
                             strong, pungent, suffocating odour.  Soluble in
                             water and ethanol.

    USE                      As an antimicrobial preservative and as an
                             anti-browning agent.


    CHEMICAL NAME            Sodium sulfite

    EMPIRICAL FORMULA        Anhydrous:  Na2SO3

                             Heptahydrate:  Na2SO3.7H2O

    MOLECULAR WEIGHT         Anhydrous:  126.05

                             Heptahydrate:  252.16

    DEFINITION               Anhydrous sodium sulfite contains not less than
                             95.0% Na2SO3.  Sodium sulfite heptahydrate    
                             contains not less than 48.0% Na2SO3.

    DESCRIPTION              Anhydrous sodium sulfite is a white powder,
                             with not more than a faint odour of sulfur
                             dioxide; 1 g is soluble in 4 ml of water. 
                             Sodium sulfite heptahydrate is a transparent or
                             white crystalline solid, with not more than a
                             faint odour of sulfur dioxide; 1 g is soluble
                             in 2 ml of water.

    USE                      As an antimicrobial preservative and as an
                             anti-browning agent.


    CHEMICAL NAME            Sodium pyrosulfite


    MOLECULAR WEIGHT         190.1

    DEFINITION               Sodium pyrosulfite contains not less then 95.0%
                             of Na2S2O5.

    DESCRIPTION              A white crystalline solid, with an odour of
                             sulfur dioxide.  1 g is soluble in 2 ml of

    USE                      As an antimicrobial preservative and as an
                             anti-browning agent.


    CHEMICAL NAMES           Sodium hydrogen sulfite; sodium bisulfite;
                             sodium acid sulfite


    MOLECULAR WEIGHT         104.06

    DEFINITION               Sodium hydrogen sulfite contains not less than 
                             95% of NaHSO3.

    DESCRIPTION              A white crystalline or granular solid, with an 
                             odour of sulfur dioxide.  1 g is soluble in 2.5
                             ml of water.

    Biological Data

    Biochemical aspects

    Sulfite is oxidized in the body to sulfate.  Bisulfite reacts with
    aldehydes and ketones, including aldehydic sugars.  This is a
    reversible reaction; the equilibrium concentrations depend on
    temperature.  The acute effects of sulfite in foods are related to the
    amount and concentration of free sulfur dioxide and to the speed at
    which the additive compounds liberate the bound sulfur dioxide.
    Sulfite may also react reversibly with disulfide linkages in proteins.
    The disulfide is split into one part containing a thiol group and
    another part with an S-sulfonic acid group.1  Sulfite reacts with
    dried yeast to form a component with anti-thiamine activity.2

    Acute toxicity

    In rabbits, the oral LD50 of sulfite, measured as SO2, was found to
    be between 600 and 700 mg/kg body-weight.3


    Animal     Route               LD50 (mg/kg body-weight)           Reference
                               Sodium bisulfite    Sodium sulfite

    Mouse      Intravenous           130                175               4
    Rat        Intravenous           115                -                 4
    Hamster    intravenous           95                 -                 4
    Rabbit     Intravenous           65                 -                 4
    In man, a single oral dose of 4 g of sodium sulfite caused toxic
    symptom in 6 of 7 persons.  In another subject, 5.8 g caused severe
    irritation of the stomach and intestine.3

    The vomiting reflex in man appeared regularly with doses of sulfite
    equivalent to less than 250 mg SO2, i.e. 3.5 mg SO2 per kg

    Short-term studies

    Rat. In thiamine-deficient rats, daily oral administration of fruit
    syrup containing 350 ppm of sulfur dioxide in a dose of 0.5 ml/150 g
    rat for 8 weeks failed to influence growth.6

    Groups of weanling rats numbering 5 per group were fed 0.6% sodium
    metabisulfite (not less than 3400 ppm as SO2) for 6 weeks.  The diets
    were either freshly sulfited or stored at room temperature before use.
    A reduction in growth occurred in rats receiving the fresh diet which
    was attributed to lack of thiamine.  Rats fed the diet which had been
    stored for 75 days developed signs of thiamine deficiency and
    additional toxic effects including diarrhoea and stunting of growth
    which could not be reversed by the administration of thiamine.2

    (Work in progress)  Three groups of 20 to 30 rats containing equal
    numbers of males and females received daily doses of sulfite dissolved
    in water or added to wine, and a control group received the same
    volume of water.  The levels of sulfite in the 2 groups receiving wine
    were equivalent to 105 mg and 450 mg SO2 per litre respectively and
    the aqueous solution contained potassium metabisulfite equivalent to
    450 mg SO2 per litre.  The effect of this treatment was studied in 4
    successive generations, the duration being 4 months in females and 6
    months in males.  Groups of animals from the second generation were
    treated for 1 year.  No effect was observed on weight gain, efficiency
    of utilization of protein, biological value of the same protein or
    reproduction.  There was also no effect on the macroscopic or
    microscopic appearance of organs or organ weights.  The only effect
    observed was a slight diminution in the rate of tissue respiration by
    liver slices in vitro.7

    (Work in progress)  About 120 rats containing equal numbers of each
    sex were divided into 2 groups, one receiving potassium metabisulfite
    equivalent to 0.6% SO2 in the drinking-water, the other group serving
    as controls.  No effect was observed after treatment for 3 months on
    reproduction, mortality or blood count.  The second and third
    generations were treated in the same way for 3 months, the only effect
    observed being a significant reduction in the size of the litters of
    treated mothers.  No effect of sulfite on digestive enzymes in vitro
    was observed at a level equivalent to 360 mg SO2 per gram of protein. 
    No effect on the incidence of dental caries in the rat was produced by
    0.5% potassium metabisulfite in the dietary regime.  Work is in
    progress on the effects of sulfite on the metabolism of thiamine,
    vitamin A and calcium.8

    Rabbit.  One rabbit given 3 g of sodium sulfite by stomach tube each
    day for 185 days lost weight, but all organs were normal post mortem.
    Two rabbits given 1.08 g daily for 127 days gained weight.  Autopsy
    showed haemorrhages in the stomach.  Three rabbits given 1.8 g daily
    for between 46 and 171 days lost weight and autopsy showed stomach

    Dog.  A dose of 3 g of sodium sulfite daily was given by stomach
    tube to a dog weighing 17 kg for 23 days.  Another weighing 34 kg was
    given 6-16 g of sodium sulfite daily for 20 days (total dose 235 g). 
    No abnormalities were observed on autopsy in the first dog, but the
    second dog had haemorrhages in several organs.  Sodium sulfite was
    given by stomach tube to 16 growing dogs in daily doses of 0.2-4.8 g
    for 43-419 days; no damage was observed in any of the dogs.  Sodium
    bisulfite was given to 2 dogs by the same method and for the same
    length of time as in the preceding experiment in daily doses of
    1.08-2.51 g.  Examination of heart, lungs, liver, kidney and intestine
    showed no damage.  A total of 91-265 g of sodium sulfite fed to 5
    pregnant dogs over a period of 60 days had no effect on the weight of
    the mothers or on the weight gain of the litters.3

    Long-term studies

    Rat.  Groups of rats numbering from 18 to 24 per group were fed
    sodium bisulfite in dosages of 0.0125%, 0.025%, 0.05%, 0.1%, 0.25%,
    0.5%, 1% or 2% of the diet for periods ranging from 1 to 2 years.  The
    rats fed 0.05% sodium bisulfite (307 ppm as SO2) for 2 years showed
    no toxic symptoms.  Sulfite in concentrations of 0.1% (615 ppm as
    SO2), or more, in the diet inhibited the growth of the rats, probably
    through destruction of thiamine in the diet.9

    Three groups of weanling rats containing 18, 13 and 19 animals
    received drinking-water containing sodium metabisulfite at levels of 0
    ppm SO2, 350 ppm SO2 and 750 ppm SO2.  Prior interaction of the
    sulfite with dietary constituents was thus prevented.  The experiment
    lasted 2´ years and extended over 3 generations of rats.  No effects
    were observed on food consumption, fluid intake, faecal output,
    reproduction, lactation or the incidence of tumours.10

    Comment on experimental studies reported

    Sufficient data are not available to indicate the lowest dosage
    causing acute effects in man or the highest dosage that will normally
    be tolerated without producing harmful effects.  The position of the
    lowest level at which sulfite produced a significant effect in the
    long-term feeding experiments in rats may have been determined by the
    destruction of thiamine and possibly other essential dietary
    components rather than by a direct action of sulfite on the animals.
    The absence of toxic effect on long-term ingestion of sulfite in the
    drinking-water (750 ppm as SO2) is consistent with this.  Although
    the toxicity of sulfite in the drinking-water was lower than that in
    the food, this was not considered sufficient evidence for alteration
    of the evaluation given previously in the Sixth Report of the Joint
    FAO/WHO Expert Committee on Food Additives.


    Level causing no significant toxicological effect in the rat

    0.05% of sodium bisulfite (= 307 ppm as SO2) in the diet, equivalent
    to 15 mg/kg body-weight per day, calculated as SO2.

    0.1% of sodium metabisulfite (= 750 ppm as SO2) in the
    drinking-water, equivalent to 37 mg/kg body-weight per day, calculated
    as SO2.

    Estimate of acceptable daily intakes for man (calculated as SO2)

                                              mg/kg body-weight

               Unconditional acceptance              0-0.35
               Conditional acceptance              0.35-1.5


    1.  Swan. J. M. (1957) Nature (Lond.), 180, 643

    2.  Bhagat, B. & Locket, M. F. (1964) Food Cosmet. Toxicol., 2, 1

    3.  Rost, E. & Franz, F. (1913) Arb. Gesundh.-Amte (Berl.), 43, 187

    4.  Hoppe, J. O. & Goble, F. C. (1951) J. Pharmacol. exp. Ther., 101,

    5.  Lafontaine, A. & Goblet, J. (1955) Arch. belges Méd. soc., 13, 281

    6.  Locket, M. F. (1957) J. Pharm. (Lond.), 9, 605

    7.  Jaulmes, P. (Unpublished report of work in progress submitted to
    WHO in 1964)

    8.  Causeret, J. (Unpublished report of work in progress submitted to
    WHO in 1964)

    9.  Fitzhugh. O. G., Knudsen, L. F. & Nelson, A. A. (1946) J.
    Pharmacol. exp. Ther., 86, 37

    10. Locket, M. F. & Natoff, I. L. (1960) J. Pharm. Pharmacol., 12, 488

    See Also:
       Toxicological Abbreviations
       Sulfur dioxide (FAO Nutrition Meetings Report Series 40abc)
       SULFUR DIOXIDE (JECFA Evaluation)