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    DIOCTYL SODIUM SULFOSUCCINATE

    First draft prepared by Dr F.S.D. Lin,
    Division of Toxicological Review and Evaluation,
    Center for Food Safety and Applied Nutrition,
    US Food and Drug Administration.

    1.  EXPLANATION

         Dioctyl Sodium Sulfosuccinate (DSS) is the dioctyl ester of
    sodium sulfosuccinate.  The pure compound is a white waxy solid,
    soluble in many organic solvents and in water.  It is an anionic
    surface active compound, which has marked wetting characteristics. 
    Its detergent properties make it useful for cleaning and peeling
    fruits and vegetables and cleaning food packaging.  It is also used
    in various pharmaceutical products.  The structure of DSS is shown
    in Figure 1.

    Figure 1.


                                        C2H5
                                        '
                               CH2COOCH2CH(CH2)3CH3
                                '
                       NaO3S - CHCOOCH2CH(CH2)3CH3
                                       '
                                       C2H5


         This food additive was reviewed at the twenty-second meeting of
    the Committee (Annex 1, reference 47), when the temporary ADI 2.5
    mg/kg/bw was withdrawn because the additional information which had
    been required by the Committee at its eighteenth meeting was not
    provided.  The required information included: (1) the effects on
    newborn animals, particularly those exposed to DSS through
    lactation:  (2) an adequate long-term study in a rodent species: and
    (3) a study of the effects of DSS on the pulmonary vascular system. 
    These data were still not available at the twenty-fourth meeting
    (1980) and the Committee did not prepare a monograph.

         Since the last evaluation of DSS additional toxicological data
    have become available to the Committee: these data are summarized
    and discussed in the following monograph.  The previously published
    monograph from the 18th meeting is also included as part of this
    monograph.

    2.  BIOLOGICAL DATA

    2.1  Biochemical Aspects

    2.1.1  Absorption, distribution, metabolism, and excretion

    2.1.1.1  Rat

         DSS labelled with 35S was administered orally in a single
    dose (50 mg/kg) in an alcohol and water (1:1 v/v) solution to albino
    rats weighing 200 g.  The animals were provided with food and water
     ad libitum.  More than 85% of the administered DSS was excreted
    within 24-48 hours post dosing and essentially all within 96-120
    hours.  25%-35% of the DSS was excreted in the urine 24-48 hours
    post dosing, then only trace amounts via this route.  The faeces
    contained over 66% of the radiolabel, indicating that the major
    route of elimination is the gastrointestinal tract.  The tissues of
    the rats 96-168 hours post dosing contained only trace amounts of
    radiolabel (Patel, 1969).

         In another study, two rats were administered orally a single
    dose of either 5 mg or 10 mg of DSS in water, and two rats a single
    dose of DSS, 10 mg by i.v. route.  A fifth rat received a single
    oral dose of 5.8 mg of 2-ethylhexanol in 40% ethanol.  In the first
    24 hour post dosing period, in animals receiving the 5 or 10 mg oral
    dose 18.6% and 15.5% of the total dose was excreted in the urine and
    0.9 and 8.7 % in the faeces.  Animals receiving DSS i.v. excreted
    12.3-15.5% in the urine in this period and none in the faeces.  The
    24-48 hour urine sample from the test animals did not contain
    detectable 2-ethylhexanol.  Rats administered 2-ethylhexanol
    excreted 3.1% of the dose in urine and 3.9% in the faeces, in the
    first 24 hours post dosing (Kelly  et al., 1973).

         One adult male rat was administered 14C labelled DSS by
    gavage, at a dose level equivalent to 10 mg/kg b.w.  64.1% of the
    administered radioactivity was excreted in the urine during the
    first 24 hours and approximately 1.0% during the 24-48 hour period. 
    37.4% and 0.9% of the administered radioactivity was excreted in the
    faeces during this period.  DSS undergoes extensive metabolism in
    the rat since no unchanged DSS appeared to be present in the urine,
    and only a small amount was present in the faeces (Kelly  et al.,
    1973).

    2.1.1.2  Rabbit

         Two female rabbits were each administered a single dose of 14C
    radiolabelled DSS (4 mg), one orally, one i.v.  Each route of
    administration resulted in the excretion of over 90% of the
    radioactivity in the urine (87% and 69.7%, 0-24 hours after dosing,
    oral and i.v., respectively).  Analyses of the 0-24 hour urine 

    sample indicated similar patterns of metabolites, irrespective of
    the route of administration (Kelly  et al., 1973).

    2.1.1.3  Dog

         Two male beagle dogs were dosed with 4 mg/kg b.w. 14C
    radiolabelled DSS, one orally, one i.v.  Analyses of blood for 2-
    ethylhexanol compounds indicated that in the case of the i.v.
    injected dog the blood level of these compounds fell off rapidly
    during the first hour and was zero at eight hours.  Oral
    administration of the DSS led to the appearance of small amounts of
    this compound in the blood after one hour, but the level was zero at
    eight hours.  Each route of administration led to similar excretion
    patterns and metabolic profile.  About 21% of the label was excreted
    in the urine in the first 24 hours, the bulk of the radiolabel being
    excreted in the faeces (about 70%) in the 24-48 hour post dosing
    (Kelly  et al., 1973).

    2.2  Toxicological studies

    2.2.1  Acute oral toxicity
                                                                      
        Species     Acute Toxicity       Reference
                    g or ml/kg/b.w.
                                                                      
         Mouse      4.8 g/kg             Hooper et al., 1949

         Mouse      2.64 g/kg            Case et al., 1977

         Mouse      1.50 g/kg            Schultz, 1941

          Rat       3.98 g/kg            Lundholm & Svedmyr, 1959

          Rat       1.80 g/kg            Olsen et al., 1962

          Rat       4.3 g/kg             Hazleton Laboratories, 1954

          Rat       3.08 g/kg            American Cyanamid, 1966

          Rat       7.5 ml/kg*           Huntingdon Research, 1977a

          Rat       5.7 g/kg*            Huntingdon Research, 1977a

          Rat       4.2 ml/kg**          Huntingdon Research, 1977b
                                                                      
    *    Compound tested was Aerosol/OT-80 PG which consists of 80% 
         DSS 20%, propylene glycol solvent and less than 1% sodium 
         sulfate.

    **   Compound tested was Aerosol OT-100 which consists of 100% DSS.

         DSS is practically nontoxic when given orally to mice and rats;
    its acute toxicity ranging from 2.64 to 5.7 g/kg bw.  In most cases,
    the gross pathological examination did not reveal any observable
    lesions except that the gastrointestinal tract of some animals that
    died were filled with clear fluid.  In addition, some animals had
    diarrhoea or showed signs of intestinal irritation.

    2.2.2  Short-term studies

    2.2.2.1  Rat

         In a 9-week study rats that received 25% of DSS in the diet
    showed a decrease in growth rate.  The authors suggested that this
    effect was due to impalatability of the DSS treated diet since this
    group showed a decrease in food consumption.  Necropsy revealed no
    visible lesions in the G.I. tract (Guerrant, 1937).

         Groups of five male and five female rats were given 0, 0.19,
    0.37, 0.55, 0.75, and 0.87 g/kg of DSS in their diet for 24 weeks. 
    No deaths occurred but there was some initial lag in body weight
    gain compared to the controls.  No significant haematological
    effects were noted.  Histology of the liver, spleen, kidney,
    pancreas, stomach, and gut, bladder, gonads, heart, lung, brain and
    spinal cord showed nothing remarkable (Benaglia  et al., 1943).

         Groups of five male weanling rats were given diets containing
    0, 2%, 4%, and 8% DSS for 16 weeks.  There was marked growth
    retardation at the 2% level without mortality, but only one animal
    survived at 4% and all animals died within one week at the 8% level
    from severe gastrointestinal distrubances (Fitzhugh & Nelson, 1948).

         Several short-term studies that were conducted in rats
    administered DSS in the diets of 28 days at dose levels up to 1%
    revealed no significant effects.  (Hazleton Laboratories, 1959).

         In a further experiment, groups of 12 male and 12 female
    weanling rats were provided with diets containing 0, 0.5% 1.04% and
    1.5% DSS for 26 weeks.  There were no significant differences
    between test and control groups regarding body weight gain with the
    exception of female animals which showed some slight reduction at
    the 1.0% and 1.5% level during the third week.  No adverse effects
    appeared in the findings of haematology, urinalysis, food
    consumption, the weight of spleen, liver, adrenal, kidney, gonads,
    or in the histology of the heart, lung, liver, spleen, kidney,
    adrenal, bladder, thyroid, pancreas, lymph nodes, gut, muscle, bone,
    marrow, gonads and thymus.  Two controls and four test animals in
    the 1.5% group died, two of the latter from haemorrhagic
    gastroenteritis (Taylor, 1966).

    2.2.2.2  Rabbit

         Seven rabbits were given intragastrically 0.124 g DSS/kg bw
    daily for 24 weeks.  Higher doses were not tolerated because of
    gastrointestinal irritation.  No abnormal pathological findings were
    seen on gross and histopathological examination of the liver,
    spleen, pancreas, kidney, gut, bladder, gonads, heart, lung and CNS
    (Benaglia  et al., 1943).

    2.2.2.3  Monkey

         Three monkeys were given intragastrically 0.125 g DSS/kg bw
    daily for 24 weeks.  Higher doses were not tolerated because of
    gastrointestinal irritation.  No abnormal pathological findings were
    seen on gross and histopathological examination of the liver,
    spleen, and pancreas, kidney, gut, bladder, gonads, heart, lung and
    CNS (Benaglia  et al., 1943).

    2.2.2.4  Dog

         When 4 male and 4 female Beagle dogs were given 30 mg/kg doses
    of DSS via gavage for a period of one year, no treatment-related
    signs of toxicity were observed at any period when the dogs were
    examined.  Gross and microscopic examination of tissues and organs
    of the G.I. tract did not reveal any toxic changes, nor were there
    any serum enzyme changes indicative of chronic liver toxicity (Case
     et al., 1977).

    2.2.2.5  Guinea pig

         Groups of 3 guinea pigs were given 0.1, 0.5, and 1.0 g/1
    solutions of DSS (Alphosol OT) as a replacement for drinking water
    for a period of 15 months.  The growth rate of the animals was not
    affected, once they were adjusted to the taste of DSS.  Necropsies
    did not reveal any pathological alterations in organs and tissues of
    the treated animals (Bengalia, 1943).

    2.2.3  Long-term/carcinogenicity studies

    2.2.3.1  Rat

         Groups of 12 male and 12 female weanling rats were given 0,
    0.25%, 0.5% and 1.0% DSS in their diet for two years.  Body weight
    gain was slightly reduced in the 1% test group during the first
    three months and became more pronounced during the first year.  No
    pathological changes were noted at gross examination or in the
    histology of lung, heart, liver, spleen, pancreas, stomach and gut,
    kidney, adrenal, testes, thyroid, parathyroid, lymph nodes, bone,
    muscle, and marrow (Fitzhugh & Nelson, 1948).

         When given orally to inbred Charles River Fischer 344 rats as
    1.0% of the diet, DSS exhibited no promotional activity in rats
    treated with s.c. injections of 1,2,-dimethylhydrazine (DMH) at 20
    mg/kg/wk for 20 weeks.  Reducing the dose of DMH to 10 mg/kg/wk
    decreased significantly the number of gastrointestinal tumours per
    rat in the DSS treated group at the 5th and 6th month necropsies
    (Karlin, 1980).

    2.2.4  Reproduction studies

    2.2.4.1  Rat

         DSS was fed in the diet to groups of 40 male and 40 female rats
    (Carworth Farms, CFE strain) for three successive generations at
    levels of 0, 0.5, or 1.0%.  Pairs of rats were mated to produce two
    litters per generation with the exception of the F1b generation
    which was bred once to produce a single F2 generation.  The F2
    generation was maintained on the test diet until three to four
    months of age before mating.  For the first mating of the F0
    generation and the F2 generation, the dams were continuously fed
    the test diets, and the pups weaned directly onto the test diets. 
    For the other three matings (F1b, F2 and F3a pups), DSS was
    removed from the diet of the dams before they were expected to cast
    their litters.  After weaning, the pups were placed on test diets. 
    Reproduction performance was evaluated in terms of fertility index,
    gestation index, viability index and lactation index.  Litter size
    was reduced to 10 pups at day 5.  Pups from all litters, including
    those which died before weaning, were examined for gross defects. 
    Autopsies were performed on pups from the first mating of the F2
    animals.  Portions of all major organs from one female and one male
    from each litter were examined histologically.  Carcasses of the
    other pups were cleared and skeletons stained and examined for
    defects.

         The first mating of the F0 generation and F2 generation (dams
    continuously fed DSS and pups weaned to test diet), resulted in
    fertility indices and gestation indices that were high and
    comparable.  The viability index was good, but slightly depressed
    for F3b pups.  The lactation index was depressed for both of these
    matings (64, 46, 42 for F1a pups at 0, 0.5, 1.0% test diet
    respectively, and 71, 59, 53 for F3b pups for the respective
    diets).  Also, for these groups, mean weight of pups decreased with
    increasing concentrations of DSS in the diet of the dams.

         For the other three matings (F1b, F2, F3a pups), the
    viability and lactation indices and the mean weight of pups from
    dams on test diets were less than those of control for the F1b
    pups, but similar to controls for the F2 and F3a pups.

         The lowering of survival rate and mean body weight of F3b pups
    was attributed to impairment of nutrition, because of the taste of
    DSS secreted in the milk of the dams.

         Autopsy and skeletal studies of the pups indicated no
    significant changes, with the exception of the occasional presence
    of an extra vertebra in the sternum between the fifth and sixth
    sternebrae (1/29, 7/30, and 4/29 at 0, 0.5 and 1% test levels of
    DSS).  This is considered to be a truly accessory sternebra, and not
    caused by parental exposure to DSS (American Cyanamid Co., 1970).

         DSS was administered to Sprague-Dawley rats at levels of 1.0 or
    2.0% in the diet on days 6 and 15 of gestation.  There were no
    effects observed at the 1% dose level.   However, at 2% DSS produced
    growth retardation in the dams, significant increase in fetal
    resorptions, and a significantly higher percentage of externally
    malformed fetuses. The external anomalies in pups that were derived
    from DSS treated dams were said to consist primarily of exencephaly
    of varying degrees of severity, and this malformation was frequently
    associated with spina bifida and microphthalmia (Hoechst Roussel
    Pharmaceuticals, 1976).

         In another study pregnant rats which received 2% DSS in the
    diet from day 6 to day 16 of gestation showed decreased maternal
    food consumption and weight gain as well as decreased fetal body
    weights and crown-rump distances compared to control groups.  In
    addition, DSS caused delayed ossification of sternebrae in the
    foetuses.  However, there was no reported incidence of exencephaly
    at the 2% dose level (Hoechst Roussel Pharmacueticals, 1979).

         Three generations of 30 male and 30 female immature Charles
    River CD Sprague-Dawley rats were fed diets containing 0, 0.1, 0.5
    or 1% DSS for 10 and 2 weeks in the parent generation, and at least
    10 weeks post weaning in successive generations.  The original
    parents, F0 animals, were mated to produce an F1 litter: F1
    animals produced F2 animals, and F3 animals were produced from F2
    animals.  In each generation the same regimen for DSS exposure was
    repeated, and the study terminated with the F3 weanlings.  All
    adults and the F3 weanlings (one/sex/litter) were necropsied and
    examined for gross lesions and abnormalies.

         There were no effects on the reproductive function of parental
    animals of either sex during any of the three generations of the
    study.  At the 1% level, body weights were lower than the controls
    during the premating period of males in all three generations and
    for F1 and F2 females.  Body weights for F1 and F2 males and
    females of the 0.5% dose group were slightly lower than controls
    during the premating period.  Pup weights on day 0 of lactation were
    lower in the treated groups than in the control group, but the
    difference was significant only for the high dose (1%) group of the

    third generation.  Lower pup weights in the 0.5 and 1% groups
    resulted in significantly lower pup weights on day 21 for all three
    generations.  Pup survival (91-100%) was comparable between treated
    and control groups of all generations.

         The above results indicate that DSS at 0.5% and 1% levels
    caused a reduction in body weight for parental males of all
    generations and for F1 and F2 females, and weanling pup weights at
    these dose levels were lower than the controls in all three
    generations.  However, there were no adverse effects on reproductive
    function of the test animals and nor were there treatment-related
    microscopic lesions or effects on antemortem function of either sex
    in any generation (MacKenzie  et al., 1990).

    2.2.5  Special studies on DSS in the gut

         It has been demonstrated that DSS within the isolated
    intestinal lumen of rats (organ bath) produced definite inhibition
    of muscular and glandular functions.  The segment of gut when
    flushed with DSS inhibited acetylcholine stimulation by 92%, and in
    the quiescent gut the inhibition was 71%.  The theory was that the
    inhibitory action of DSS was mediated by a hormone released from the
    intestinal mucosa (Lish, 1961).

         When tested on isolated rabbit jejunum in an organ bath, DSS
    had a distinct inhibitory effect on pendular movements at a
    concentration of 0.7 mg/ml; at a concentration of 7 mg/ml these
    movements were virtually suppressed (Lundholm & Svedmyr, 1959).

         In a study on isolated ileum and colon of 14 male Sprague
    Dawley rats, DSS induced the secretion of water and sodium and
    increased the short circuit current in 13 of 14 preparations.  It
    was thought that the actions were mediated by mucosal cyclic
    adenosine monophosphate (Donowitz 1975).

         When segments of human and rat small and large intestines were
    given DSS in concentrations of which may be obtained when fed to
    humans at 0.5mM, DSS blocked water absorption.  In human jejunum the
    inhibition was 80%.  In the rat jejunum, ileum and colon the degree
    of inhibition was linear with the concentration of DSS (Saunders,
     et al., 1975).

         In a study where portions of jejunum of Sprague-Dawley rats
    were exteriated and a section was delineated with sutures, DSS was
    applied to the serosa at various concentrations.  Thirty days post
    treatment samples were taken of the treated and untreated guts and
    the number of ganglion cells were counted.  The results showed that
    there were ganglion loss in the DSS treated areas of 0.01, 0.1 and
    1.0% with the loss rate compared to untreated as 61%, 85%, and 100%,
    respectively.  It was concluded that DSS ablated the myenteric

    neurons leading to a depletion of peptidergic neurons and an
    alteration in the electrical parameters of the gut (Fox  et al.,
    1983).

    2.2.6  Special studies on the laxative action of DSS

         In studies with normal rats, as well as those with a tendency
    to constipation induced by opium drugs, DSS potentiated the effects
    of laxatives containing anthraquinone derivatives (Lundholm &
    Svedmyr, 1959).

    2.2.7  Special studies on pulmonary circulatory system

    2.2.7.1  Rabbit

         When rabbits were exposed to an aerosol containing 5% DSS in
    95% ethanol and isotonic saline the pulmonary clearance of
    technetium-99m-labeled diethylenetriamine pentaacetate (99m-Tc-DPTA)
    from aveoli to blood was accelerated by DSS without affecting gas
    exchange or lung mechanics.  (Evander  et al., 1987).

         In a second study 56 mongrel dogs were evaluated for the
    effects of DSS on pulmonary oedema.  In the study, DSS was
    administered as a 1% aerosol in 95% ethanol and isotonic saline. 
    Two hours post treatment the pulmonary extravascular water volume
    was increased indicating that there was a loss of surfactant
    activity and an increase in alveolar surface tension (Nieman  et
     al., 1985).

         Neither of the above studies on the activity of DSS in the lung
    is considered relevant to the safety evaluation of DSS as a direct
    food additive.

    2.3  Observation in humans

         DSS has been used as a faecal softener in a large number of
    cases for many years since 1943 in infants, children and adults
    (Wilson & Dickinson, 1955).

         In chronic constipation it is used as a non-laxative softener
    but action does not become apparent for one to two days after taking
    it.  Dosage employed is 10-20 mg daily for infants and children, 10-
    60 mg daily for adults, exceptionally 100 mg/day.  Up to 300 mg can
    be taken without adverse effects (Anon, 1956).  Others have
    suggested 50 mg/day as optimum (Fairing & Short, 1956).

         Two human subjects were given 200 mg/kg of DSS orally.  Peak
    concentrations in the serum occurred two hours post dosing, and
    concentrations of DSS found in the plasma of the subjects were
    similar to those observed in dogs one hour after an oral dose 4
    mg/kg (Kelly  et al., 1973).

         When patients with T-tube biliary drainage were given doses of
    100 mg or 200 mg DSS orally the results of gas chromatography
    analysis indicated that DSS was present in the bile at
    concentrations of 2 to 4 x 10-5M (Dujovne & Shoemans, 1972).

         In a human panel where drugs were prescribed to 6,937 women
    during the first trimester of pregnancy, 473 received DSS
    (docusatesodium), and only one gave birth to a child with
    unspecified congenital disorder (Jick  et al., 1981).

    3.  COMMENTS

         The Committee noted that results from a three-generation
    reproduction study with DSS in rats did not reveal any adverse
    effects on the reproductive function of either sex at dose levels up
    to 10 g/kg in the diet.  Neither was there any evidence of adverse
    affects on the offspring both as a result of prenatal and postnatal
    exposure to DSS.  However, DSS did cause a reduction in parental
    body weight as well as weanling pup weight at dose levels of 5 g/kg
    and above in the diet. It was concluded that the no-observed-effect
    level of DSS was 1 g/kg in the diet, equivalent to 50 mg per kg of
    body weight per day.

         In a long-term study, DSS did not exhibit tumour promotional
    activity in rats pre-exposed to a model gastrointestinal carcinogen. 
    However, a full carcinogenicity bioassay that meets modern standards
    is still lacking.

         Two inhalation studies in which rabbits and dogs were exposed
    to DSS were reviewed by the Committee.  No adverse pulmonary or
    systemic effects were indicated from the results.

    4.  EVALUATION

         The Committee based its evaluation of DSS on the no-observed-
    effect level found in the three-generation reproduction stduy in
    rats, to which a safety factor of 200 was applied.  A temporary ADI
    of 0-0.25 mg per kg of body weight was allocated to DSS, pending the
    evaluation, in 1995, of the results of the long-term study in a
    rodent species that was requested earlier.

    5.  REFERENCES

    AMERICAN CYANAMID CO. (1966).  Toxicity Data sheet for Dioctyl
    Sodium Sulfosuccinate.  Unpublished data.  Submitted to WHO by
    American Cyanamid Co.

    AMERICAN CYANAMID CO. (1970).  Report on Aerosol OT, Successive
    Generation studies in rats.  Unpublished report.  Submitted to WHO
    by American Cyanamid Co.

    ANON. (1956).  Dioctyl sodium sulfosuccinate, U.S.P.,  J. Am. Med.
     Assoc., 161, 65.

    BENGALIA, A.E., UTLEY, E. & CLEVERDON, M.A. (1943).  The chronic
    toxicity of Aerosol-OT.   J. Ind. Hyg. Toxicol., 25, 175-180.

    CASE, M.T., SMITH, J.K., & NELSON, R.A. (1977).  Acute mouse and
    chronic dog toxicity studies of danthron, dioctyl sodium
    sulfosuccinate, poloxalkol and combinations.   Drug Chem. Toxicol.,
    1, 89-91.

    DONOWITZ, M. (1975).  Effect of DSS on colonic fluid and electrolyte
    movement.   Gastroenterol., 69, 941-958.

    DUJOVNE, C.A. & SHOEMAN, D. (1972).  Liver culture toxicity and
    human biliary excretion of the components of an hepatotoxic laxative
    preparation.   Gastroenterol., 62, 172.

    EVANDER E., WOLLMER, P. & JONSON, B. (1988).  Pulmonary clearance of
    inhaled 99m Tc-DTPA:  Effect of the detergent dioctyl sodium
    sulfosuccinate.   Clin. Physiol., 8, 105-111.

    FAIRING, J.P. & SHORT, F.R. (1956).  Spectrophotometric
    determination of alkybenzene sulfonate detergents in surface water
    and sewage.   Anal. Chem., 28, 1827-1834.

    FITZHUGH, O.G. & NELSON, A.A. (1948).  Chronic oral toxicities of
    surface active agents.   J. Amer. Pharm. Assoc. Sci., 37, 29-32.

    FOX, D.A., EPSTEIN, M.L. & BASS, P. (1983).  Surfactants selectively
    ablate enteric neurons on rat jejunum.   J. Pharm. Exp. Therap.,
    227, 538-544.

    GAGINELLA, T.S., HADDAD, A.C., GO, V.L.W. & PHILLIPS, S.F. (1977). 
    Cytotoxicity of ricinoleic acid (castor oil) and other detergents on
    intestinal epithelial cells.  J. Pharm. Exp. Therap., 201, 259-265.

    GUERRANT, N. (1937).  The toxicity of Alphasol.  Unpublished Report
    to American Cyanamid.  Submitted to WHO by American Cyanamid Co.

    HAZLETON LABORATORIES (1954).  Aerosol OT-Toxicity Report (Sodium
    Di-N-Octyl Sulfosuccinate).  Interoffice correspondence to J.P.
    McPherson, American Cyanamid Co.  Submitted to WHO by American
    Cyanamid Co.

    HOECHST ROUSSEL PHARMACEUTICALS INC. (1976).  Pharmacologist Review
    of NDA 10-586.  (Annual Report of Aug. 1973).

    HOLLANDER, L. (1953).  Unpublished report to D.O. Hamlin. American
    Cyanamid Co.  Submitted to WHO by American Cyanamid Co.

    HOOPER, S.S., HULPREN, H.R. & COLE, V.V. (1949).  Some toxicological
    properties of surface active agents.  J. Am. Pharm. Assoc., 38,
    428-432.

    HUNTINGDON RESEARCH CENTER (1977a).  Limited Release Toxicity Tests
    Aerosol OT-80-PG.  Unpublished report to American Cyanamid. 
    Submitted to WHO by American Cyanamid Co.

    HUNTINGDON RESEARCH CENTER (1977b).  Limited Release Toxicity Tests
    Aerosol OT-80-PG.  Unpublished report to American Cyanamid. 
    Submitted to WHO by American Cyanamid Co.

    JICK, H., HOLMES, L.B., HUNTER, J.R., MADSEN, S. & STERGACHIS, A.
    (1981).  First trimester drug use and congenital disorders.  J. Am.
     Med. Assoc., 246, 343-346.

    KARLIN, D.A., O'DONNELL, R.T. & JENSEN, W.E. (1980).  Effect of
    dioctyl and sodium sulfosuccinate feeding on colorectal 1,2-
    dimethylhydrazine carcinogenesis.   J. Natl. Cancer Inst., 64, 791-
    793.

    KELLY, R.G., FLOYD, H.A., JOLLY, E.R. & TOVE, P.A. (1973).  The
    pharmacokinetics and metabolism of dioctyl sodium sulfo-succinate in
    several animal species and man.  Internal report of Lederle
    Laboratories, American Cyanamid.  Submitted to WHO by American
    Cyanamid Co.

    LISH, P.M. (1961).  Some pharmacological effects of dioctyl sodium
    sulfosuccinate on the gastrointestinal tract of the rat. 
     Gastroenterol., 41, 580-584.

    LUNDHOLM, L. AND SVEDMYR, N. (1959).  The influence of dioctyl
    sodium sulfosuccinate on the laxative action of some anthraquinone
    derivatives.   Acta Pharm. Tox., 15, 373-383.

    MacKENZIE, K., HENWOOD, S., FOSTER, G., AKIN, F., DAVIS, R.,
    DEBAECKE, P., SISSON, G., & MCKINNEY, G. (1990).  Three-Generation
    Study with Dioctyl Sodium Sulfosuccinate (DSS) in rat.   Fund. Appl.
     Toxicol.,  (In press).

    NIEMAN, G.F., & BRENDENBERG, C.E. (1985).  High surface tension
    pulmonary oedema produced by detergent aerosol.   J. Appl. Physiol.,
    58, 129-136.

    OLSON, K.J., DUPREE, R.W., PLOMER, E.T., & ROWE, V.K. (1962). 
    Toxicology properties of several commercially available surfactants.
     J. Soc. Cosmet. Chem., 13, 469-476.

    PATEL, Y.M. (1969). Excretion of orally administered Dioctyl Sodium
    Sulfosuccinate (DSS) in rats using Sulfur-35 tagged materials. 
    Inter office Correspondence to Dr. Cantrell.  American Cyanamid,
    Pearl River, N.J. Submitted to WHO by American Cyanamid Co.

    SAUNDER, D.R., SILLERY, J. & RACHMILEWITZ, D. (1975).  Effect of
    dioctyl sodium sulfosuccinate on structure and function of rodent
    and human intestines.   Gastroenterol., 69, 380-386.

    SCHULTZ, F.H. Jr. (1941).  Personal Communication. Quoted in 18th
    report of the Joint FAO/WHO Expert Committee on Food Additives.

    TAYLOR, R.E. (1966). Report from Harris Laboratories dated
    1/22/66.b.  Submitted to WHO by American Cyanamid Co.

    WILSON, J.L. & DICKINSON, D.G. (1955).  Use of dioctyl sodium
    sulfosuccinate (Aerosol O.T.) for severe constipation.   J. Am. Med.
     Assoc., 158, 261.


    See Also:
       Toxicological Abbreviations