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    PROPYLENE GLYCOL ALGINATE

    First draft prepared by
    Dr G.J.A. Speijers and Mrs M.E. van Apeldoorn
    National Institute of Public Health and Environmental Protection
    Laboratory for Toxicology
    Bilthoven, The Netherlands

    1.  EXPLANATION

         Alginates are polyuronic acids which are major components of
    the cell walls of brown seaweed.  Brown seaweeds have been used in
    food and feed for centuries but it is only since 1929 that alginates
    have been manufactured on an industrial scale.  Alginates have
    valuable rheological properties which can be varied to a great
    extent by varying the degree of polymerisation of the polysaccharide
    or by changing the ionic environment.  Thus alginates can provide
    solutions having a range of viscosities or gels of varying
    rigidities which may be used as texture modifiers in a wide range of
    food and industrial applications (Martin, 1986).

         Propylene glycol alginate is a reaction product of propylene
    oxide and alginic acid (Steiner & McNeely, 1951).  This substance
    was evaluated at the thirteenth, fifteenth, and seventeenth meetings
    of the Committee (Annex 1, references 19, 26, and 32).  At the
    seventeenth meeting an ADI for propylene glycol alginate of 0-25
    mg/kg bw was allocated, based on a NOEL of 2 500 mg/kg bw/day in a
    long-term toxicity study in rats.  At that meeting the Committee
    concluded that only the propylene glycol moiety is absorbed and
    metabolized, and that the alginate moiety is excreted unchanged in
    the faeces of rats and mice.  Accordingly, the Committee decided
    that the contribution of propylene glycol alginate to total dietary
    propylene glycol intake from all sources should be included in the
    ADI for propylene glycol, which was allocated an ADI of 0-25 mg/kg
    bw (Annex 1, reference 32).

         Alginic acid and its ammonium, calcium, potassium, and sodium
    salts were evaluated by the Committee at its thirty-ninth meeting
    (Annex 1, reference 101) when a group ADI "not specified" was
    allocated.

         At its present meeting, the Committee evaluated new data from a
    30-day study in rats, genotoxicity assays, a teratogenicity study in
    rabbits and a study in human volunteers.  The previously published
    monographs have been expanded and are reproduced in their entirety
    below.

    2.  BIOLOGICAL DATA

    2.1  Biochemical aspects

    2.1.1  Absorption, distribution and excretion.

          In vitro hydrolysis studies with propylene glycol alginate in
    simulated gastric juice and simulated intestinal juice showed no
    hydrolysis in simulated gastric juice, while intestinal juice
    hydrolyzed 25% in 4 hours, 65% in 12 hours and 80% in 24 hours
    (McNeely & Shepherd, 1966).

         Five grams of propylene glycol alginate/kg bw (as a 10% aqueous
    solution), labeled with 14C in the alginate moiety, or 1 g of
    propylene glycol alginate/kg bw (as a 5% aqueous solution), labeled
    with 14C in the propylene glycol moiety, was administered as a
    single dose to mice (8/group) by gavage.  Absorption, distribution
    and excretion of radioactivity were followed from 1 hour to 5 days
    after administration by whole body autoradiography.

         Some, but not all, of the label (labeled in the propylene
    glycol moiety) in a single dose of 1 g propylene glycol alginate/kg
    bw was absorbed.  The unabsorbed portion was excreted in the faeces
    within 3 days while the absorbed radioactivity was distributed
    rapidly over the whole body, was concentrated in the liver and was
    completely removed from all tissues in 3-4 days.  These findings are
    consistent with the fate of absorbed radioactivity from labeled free
    propylene glycol and its metabolites.  Five days after
    administration of 5 g propylene glycol alginate (labeled in the
    alginate moiety)/kg bw traces of radioactivity were still noted in
    the rectum.  It was concluded that released propylene glycol was
    absorbed and metabolized by the usual pathways (to acetate, lactate
    or glycogen) and had disappeared completely from the body after five
    days.  The alginate moiety and the unhydrolyzed propylene glycol
    alginate were not absorbed from the gastrointestinal tract, but
    excreted in the faeces (Sharratt & Dearn, 1972).

    2.1.2  Biotransformation

         No information available.

    2.1.3  Effects on enzymes and other biochemical parameters

         No information available.

    2.2  Toxicological studies

    2.2.1  Acute toxicity studies

         The results of acute toxicity studies with propylene glycol
    alginate are summarized in Table 1.

    Table 1.  Acute toxicity studies - propylene glycol alginate

                                                                

    Animal         Route        LD50         Reference
                             (mg/kg bw)
                                                                

    mouse          oral        7 800         FDRL, 1976

    rat            oral        7 200         FDRL, 1976

    hamster        oral        7 000         FDRL, 1976

    rabbit         oral        7 600         FDRL, 1976
                                                                

    2.2.1.1  Rats

         Groups of 60 rats were dosed with 5 g/kg bw propylene glycol
    alginate by gavage or were fed a diet containing 50 to 70% propylene
    glycol alginate for 24 hours.  No adverse effects were observed. 
    Autopsy 14 days after treatment did not reveal compound-related
    abnormalities (Woodard Res. Corp., 1972).

         Rats given 10 g propylene glycol alginate/kg bw orally as a
    suspension in corn oil showed a transient depression.  No other
    effects were noted (Newell & Maxwell, 1972).

    2.2.1.2  Rabbits

         Rabbits receiving an application of propylene glycol alginate
    as an aqueous paste on abraded skin or receiving an ocular
    application of dry powdered propylene glycol alginate did not reveal
    signs of irritation (Woodard Res. Corp., 1972).

         Rabbits injected intravenously, intraperitoneally,
    intramuscularly or subcutaneously with 6.2, 12.5 or 25 mg propylene
    glycol alginate/kg bw showed neither effects at the injection site
    nor any systemic effects (Steiner & McNeely, 1951).

         Rabbits injected subcutaneously or intramuscularly with up to
    2 ml of a sterile aqueous 2% solution of propylene glycol alginate
    did not show gross or histological abnormalities at the injection
    site.  Intraperitoneal and intravenous injections of similar amounts
    did not produce abnormal systemic effects (Ouer  et al., 1935).

    2.2.2  Short-term toxicity studies

    2.2.2.1  Rats

         Two groups of 6 female rats received a diet containing 21.5%
    propylene glycol alginate and 21.5% glucose or a normal diet
    containing 21.5% glucose for 4 weeks.  After 4 weeks of treatment 2
    animals/group were killed and the remaining 4 animals/group received
    a normal diet for an additional 4 weeks.  Thereafter the original
    control group received a diet containing 21.5% propylene glycol
    alginate and the original test group received a control diet for 2
    weeks.  The test group showed slight growth retardation but
    appearance and behaviour were normal.  Faeces of the test group were
    slimy.  Histopathogy of liver, kidneys and intestine of the 2
    animals/group that were killed after the initial 4 weeks treatment
    time did not reveal abnormalities (MRCL, 1951).

         Fifteen male rats received 5% (w/w) propylene glycol alginate
    in the diet for 30 days.  No diarrhoea was seen and bowel habit was
    normal.  Urinalysis did not reveal abnormalities.  All rats showed
    distension of the caecum, 5 rats showed distension of a portion of
    the ileum.  Twelve rats showed distension of the colon to some
    degree, with soft contents.  Soft ill-formed faecal pellets were
    seen in 10 rats. No further macroscopic changes were seen. 
    Histopathology was not carried out (Anderson  et al., 1991).

    2.2.2.2  Guinea-pigs

         Four groups of 3 guinea-pigs received 0, 5, 10 or 15% propylene
    glycol alginate in their diet for 26 weeks.  Body weight gain was
    reduced in test groups but mean food intake was similar to controls. 
    Histopathology of various organs revealed no significant lesions
    (Nilson & Wagner, 1951).

    2.2.2.3  Cats

         Eight experimental cats and one control cat were fed 0, 5, 10
    or 15% propylene glycol alginate in a diet of dog food and canned
    salmon daily for 88-111 days.  Test animals had difficulties in
    swallowing and eating because of the physical texture of the diet. 
    The animals could not eat more than 100 g dog food and 30 g canned
    salmon/day and thus lost weight.  At dietary levels of 10 and 15%
    the cats showed frequent soft stools.  Macroscopy and microscopy did
    not reveal abnormalities (no details) (Nilson and Wagner, 1951).

    2.2.2.4  Chickens

         4 Groups of 13-day old chickens (number/group unknown) received
    0, 5, 10 or 15% propylene glycol alginate in their diet for 3-7
    weeks.  At all dose levels growth rate was reduced due to
    difficulties with the diet.  Histopathology showed slight transient

    tissue changes in controls as well as test animals (no details)
    (Nilson & Wagner, 1951).

    2.2.2.5  Dogs

         Three groups of 3 male and 3 female Beagle dogs received a diet
    containing 0, 5 or 15% propylene glycol alginate for one year. 
    Stool conditions were variable at the 15% dietary level.  Weight
    gain and food consumption were normal.  No effects on haematological
    (no details) parameters or serum urea nitrogen, serum alkaline
    phosphatase, blood glucose or urinalysis (no details) were seen. 
    Organ weights (10) were comparable to controls.  Histopathology
    (21 tissues) did not reveal compound-related changes (Woodard,
    1959).

    2.2.3  Long-term toxicity/carcinogenicity studies

    2.2.3.1  Mice

         Four groups of 10 mice (bw 12-18 g) received 0, 5, 15 or 25%
    propylene glycol alginate in their diet for 12 months.  At week 39
    one control mouse and one mouse of the group fed 15% in their diet
    were killed.  In the 25% group, increased mortality, a decreased
    maximum body weight, decreased food intake and increased water
    consumption were seen.  At the 15% dose level a slightly decreased
    maximum body weight and a slightly decreased food intake were seen. 
    The effects were probably due to increased water absorption of the
    diet which caused enough bulk to limit food intake (Nilson & Wagner,
    1951).

    2.2.3.2  Rats

         Four groups of 10 male and 10 female rats (age 4 weeks)
    received during their life span 0, 5, 15 or 25% propylene glycol
    alginate in their diet.  At dose-levels of 15 and 25% in the diet
    lifespan was slightly reduced and decreased food consumption was
    seen.  Death of rats in control as well as test groups was usually
    due to myocardial fibrosis, pneumonia and the multiplicity of
    cumulative processes associated with aging.  There were no lesions
    attributed to toxaemia or to local irritative intestinal effects. 
    The bulky diets caused loose and smeary faeces and weight gain was
    reduced, probably due to inanition.  Organ weights were not
    determined.  Histopathology of major tissues (liver, kidneys,
    spleen, heart, brain, lung, stomach, small intestines, large
    intestines, ovaries/testes) did not reveal abnormalities.  A fifth
    group received 15% propylene glycol alginate in a different basal
    diet.  This group showed an increased food and water consumption. 
    Faeces were normal in this group.  The group was killed after 37
    weeks (Nilson & Wagner, 1951).

         Groups of 20 male and 20 female rats received 0% or 5%
    propylene glycol alginate in their diet for 2 years as the parent
    generation of a multigeneration study.  Two male and two female
    rats/group were killed after one year for histopathology.  After 2
    years survival of this F0 generation was 67% for males and 78% for
    females in the control group and 56% for males and 58% for females
    in the test group.  Survival time was 761 days.  No difference from
    controls in general condition, general behaviour, skin, hair, eyes,
    mean body weight, or haematology (4 males and 4 females/group) was
    seen.  Gross pathology and histopathology of 6 major organs did not
    reveal treatment-related effects (Morgan, 1959).

    2.2.4  Reproduction studies

    2.2.4.1  Rats

         Groups of 20 male and 20 female rats received 0 or 5% propylene
    glycol alginate in their diet.  After 5-6 months some animals were
    mated to produce an F1 generation.  7 Males and 7 females were F1
    controls and 10 males and 10 females the test group.  The F1
    generation was fed on similar diets and mated after 4 months to
    produce the F2 generation.  The F2 generation consisted of 9 male
    and 10 female controls and 9 male and 10 female test animals and
    were also kept on similar diets.  F0 generation survived 761 days,
    while F1 and F2 generation were killed after 202 and 212 days,
    respectively.

         No differences from controls were noted regarding mortality,
    general condition, mean body weight, fertility, gestation data,
    lactation and survival for the F1 and F2 generation.  Haematology
    was performed in the F2 generation only and did not show
    abnormalities.  Organ weights were not determined.  Gross pathology
    and histopathology of 6 major organs did not show abnormalities
    (Morgan, 1959).

    2.2.5  Special studies on genotoxicity

         The results of genotoxicity studies are summarized in Table 1.

    2.2.6  Special studies on teratogenicity

    2.2.6.1  Mice

         Groups of 22-32 pregnant albino CD-1 mice received daily from
    day 6 to 15 of gestation 0, 8, 36, 170 or 780 mg propylene glycol
    alginate/kg bw/dy by gavage as a suspension in corn oil.  Up to 170
    mg/kg bw/dy there was no effect on nidation or maternal or fetal
    survival.  The number of abnormalities seen in either soft or
    skeletal tissues did not differ from the number occurring
    spontaneously in controls.  At 780 mg/kg bw/dy maternal toxicity

    resulted in 7/32 deaths.  Surviving dams and fetuses carried to term
    appeared normal in all respects (FDRL, 1972).

    2.2.6.2  Rats

         Groups of 24 pregnant Wistar rats receved daily by gavage from
    day 6 to 15 of gestation 0, 7, 33, 155 or 720 mg propylene glycol
    alginate/kg bw/dy as a suspension in corn oil.  On day 20 Caesarean
    section was carried out and dams and fetuses were examined for
    pathological and teratological effects.  No compound-related effects
    were observed (FDRL, 1972).


        Table 1.  Results of genotoxicity assays on propylene glycol alginate

                                                                                                                                         

    Test system                Test object                      Dose-levels                  Results         References

                                                                                                                                         

    Ames test                  Salmonella typhimurium           up to 10 mg/plate            neg1            Ishidate  et al., 1984
                               (6 strains)

    Ames test                  Salmonella typhimurium           5% w/v                       negative2       SRI, 1972
                               (2 strains)

    Ames test                  Salmonella typhimurium           up to 0.60%                  negative1       LBI, 1975
                               (3 strains)

    Mitotic recomb.            Saccharomyces cerevisiae D-3     up to 1% w/v                 negative2       SRI, 1972

    Mitotic recomb.            Saccharomyces cerevisiae D4      2.5, 5.0 and 10%             negative1       LBI, 1975

    Host-mediated assay        Salmonella typhimurium           oral doses to mice           negative        SRI, 1972
                               TA 1530 and G46 i.p. in          for 1-5 days up to
                               mice                             5 g/kg bw

    Host-mediated assay        Sacharomyces cerevisiae          oral doses to mice           negative        SRI, 1972
                               D-3 i.p. in mice                 for 1-5 days up to
                                                                5 g/kg bw

    Chromosomal aberration     Chinese hamster fibroblasts      up to 1.0 mg/ml              negative2       Ishidate  et al.,
    assay                      (CHL cells)                                                                   1984; 1988

    Chromosomal aberration     human WI-38 cells                up to 1.0 mg/ml              negative2       SRI, 1972
    assay
                                                                                                                                         

    Table 1 (contd)

                                                                                                                                         

    Test system                Test object                      Dose-levels                  Results         References

                                                                                                                                         

    Micronucleus assay         rat bone-marrow                  once orally 0.03,            negative        SRI, 1972
                                                                2.5, or 5.0 g/kg bw
                                                                or daily for 5 days
                                                                0.03, 2.5 or 5.0 g/kg bw

    Dominant-lethal assay      rats                             once orally 0.03, 2.5,       negative        SRI, 1972
                                                                or 5.0 g/kg bw or daily
                                                                for 5 days 0.03, 2.5 or
                                                                5.0 g/kg bw
                                                                                                                                         

    1  Assay without and with metabolic activation.
    2  Assay without metabolic activation.
    

    2.2.6.3  Hamsters

         Groups of 20 to 23 pregnant golden hamsters received daily by
    gavage from day 6 to 10 of gestation 0, 7, 33, 150 or 700 mg
    propylene glycol alginate/kg bw/dy as a suspension in corn oil.  On
    day 14 Caesarean section was carried out.  There was no evidence of
    maternal toxicity or effect on reproduction.  Examinations of
    fetuses did not reveal compound-related abnormalities (FDRL, 1974a).

    2.2.6.4  Rabbits

         Groups of 10 to 15 pregnant rabbits received daily by gavage
    from day 6-18 of gestation 0, 8, 37, 173 or 800 mg propylene glycol
    alginate/kg bw/dy as a suspension in corn oil.  On day 29 Caesarean
    section was carried out.  No differences with respect to number of
    corpora lutea, implantation sites, resorption sites, number of live
    and dead fetuses or fetal weights were seen.  Gross examination of
    the fetuses did not reveal external congenital abnormalities. 
    Visceral and skeletal examination of fetuses from dosed does did not
    show any differences compared to control fetuses (FDRL, 1974b).

    2.2.7  Special studies on bacteriology

         Two rats were fed control diet during 6 months, thereafter they
    received 5% polyethylene glycol alginate in their diet for 3 weeks
    followed by 2 weeks on control diet.  Bacteriological examination of
    the intestinal flora showed lower counts of lactobacilli and aerobes
    but an increased count of coliforms compared to controls.  The
    anaerobic counts were comparable with those of controls (Woodard,
    1959).

    2.3  Observations in humans

         Fifty individuals known to be allergic to numerous substances
    were tested intradermally with various dilutions of propylene glycol
    alginate.  Fifty other individuals without an allergic history or
    family history of allergy were used as controls.  11 Individuals
    showed slight to moderate skin reactions (8 in test group, 3 in
    control group).  When five of those showing the greatest reactions
    (all in test group) were fed propylene glycol alginate three showed
    mild allergic reactions which were duplicated in repeated tests. 
    Three control individuals, who showed very slight skin reactions,
    did not react to oral administration of propylene glycol alginate
    (Ouer, 1949).

         Five healthy male volunteers received 175 mg propylene glycol
    alginate/kg bw/day orally for 7 days, followed by 200 mg/kg bw/dy
    for a further 16 days.  The daily doses were consumed in three
    measured portions at intervals each day.  The portions were prepared
    by adding the weighed aliquots of propylene glycol alginate with
    rapid stirring to 220 ml cold distilled water.  The hydrocolloid was

    then allowed to hydrate for 24 h to a thick but fluid gel to which
    each volunteer added a pre-determined amount of orange juice prior
    to consumption.  The treatment period was preceeded by a 7-day
    initial control period during which daily an amount of orange juice,
    equal to that to be used later, was consumed.  During the treatment
    period enquiries were made with respect to apparent allergic
    responses.  At day 3 of the initial control period, on the last day
    the of 23-day treatment period and on the last day of the 7-day
    recovery period the following parameters were examined; fasting
    blood glucose, plasma insulin, breath hydrogen concentrations,
    haematological parameters (Hb, Hct, MCV, MCH, MCHC, Er, Leu, Diff,
    platelets) and biochemical parameters (Na, Cl, K, CO2, urea, LDH
    [lactate dehydrogenase], ASAT, bilirubin, alk.  phosphatase,
    phosphate, Ca, protein, albumin, creatinine, urate, lipids,
    cholesterol, HDL cholesterol and triglycerides).  Routine urinalysis
    was carried out during the initial control week and during the third
    week of treatment.  Five-day faecal collections were made during
    days 2-6 of the initial control period and during days 16-20 of the
    treatment period.  Faecal transit time, wet wt., dry wt., water
    content, pH, occult blood, neutral sterols, fat, volatile fatty
    acids and bile acids in faeces were determined.  No allergic
    reactions were observed.  Propylene glycol alginate exerted no
    significant effects on faecal parameters (pH, water content, wet and
    dry wts.)  Faecal transit time was constant in 3 volunteers,
    increased in one and decreased in one.  Faecal total and individual
    volatile fatty acids and total and individual bile acids did not
    show changes.  Faecal total neutral sterols and cholesterol
    decreased in each volunteer.  Haematological, biochemical and
    urinary parameters did not show significant changes (Anderson
     et al., 1991).

    3.  COMMENTS

         An  in vitro study showed partial hydrolysis of propylene
    glycol alginate  in simulated intestinal juice (25% within 4 hours;
    80% within 24 hours).  Partial hydrolysis was also observed in an
     in vivo mouse study.  Absorption, distribution, and excretion
    studies in mice showed that unhydrolysed propylene glycol alginate
    and the alginate moiety were not absorbed.  Released propylene
    glycol was rapidly absorbed and metabolized to lactic and pyruvic
    acids.

         In various short- and long-term toxicity studies, 10% or higher
    propylene glycol alginate in the diet caused reduced growth
    accompanied by reduced food consumption and loose stools, the common
    effects in animals fed high doses of bulking agents.

         In a long-term toxicity study in mice (12 months) as well as in
    long-term toxicity studies in rats (> 2 years) the NOEL was 5%. 
    There was no indication of a carcinogenic effect.  Propylene glycol
    alginate did not induce gene mutations in bacteria or in yeast cells
    or chromosomal aberrations in mammalian cells  in vitro or  in
     vivo.

         In addition, in a 2-generation reproduction study in rats, 5%
    propylene glycol alginate in the diet did not cause any effects. 
    Teratogenicity studies in rats, mice, hamsters and rabbits did not
    reveal any teratogenic activity of propylene glycol alginate at dose
    levels of up to 800 mg/kg bw/day.

         No adverse effects were observed in a recent 23-day study in
    five human volunteers in which the substance was given orally at a
    dose of 200 mg/kg bw/day.

    4.  EVALUATION

         The Committee noted that similar effects - reduced growth, and
    loose stool - have been observed in animal studies with other poorly
    absorbed compounds (including modified cellulose, polyalcohols,
    gums, modified starches and other alginates).  The Committee
    reiterated that the ADI for propylene glycol alginate is limited
    only by the amount of propylene glycol that might be released. 
    Propylene glycol alginate containes up to 36% propylene glycol.  On
    the assumption that all of this amount is hydrolyzed, and taking
    into account the ADI of 0-25 mg/kg by for propylene glycol, the
    Committee allocated an ADI of 0-70 mg/kg bw (100/36 x 25) to
    propylene glycol alginate.

         The Committee was aware of new toxicological studies on
    propylene glycol, but as the compound was not on the agenda, the
    data were not reviewed.  The Committee recommended that propylene
    glycol be reviewed at a future meeting.  Because the ADI for
    propylene glycol alginate is based on the ADI for propylene glycol,
    the Committee also recommended that the former substance be
    reconsidered at the same meeting.

    5.  REFERENCES

    ANDERSON, D.M.W., BRYDON, W.G., EASTWOOD, M.A. & SEDGWICK, D.M.
    (1991) Dietary effects of propylene glycol alginate in humans.
     Fd. Add. Contam.  8 (3), 225-236

    FDRL (1972) Food and Drug Research Laboratories Inc. Report on
    teratologic evaluation of PGA.  PB-221 786.  Submitted to WHO by
    Marinalg International, Paris, France.

    FDRL (1974a) Food and Drug Research Laboratories Inc.  Report on
    teratologic evaluation of PGA in hamsters.  PB-221 786.  Submitted
    to WHO by Marinalg International, Paris, France

    FDRL (1974b) Food and Drug research Laboratories Inc.  Report on
    teratologic evaluation of compound FDA 71-18.  Propylene glycol
    alginate in rabbits.  PB-267 196.  Submitted to WHO by Marinalg
    International, Paris, France.

    FDRL (1976) Food and Drug Research Laboratories Inc.  Paper No. 124,
    as summarized in RTECS.  Submitted to WHO by Marinalg International,
    Paris, France.

    ISHIDATE, Jr., M., SOFUNI, K., YOSHIKAWA, K., HAYASHI, M., NOHMI,
    T., SAWADA, M. AND MATSUOKA, A. (1984) Primary mutagenicity
    screening of food additives currently used in Japan.   Fd. Chem.
     Toxicol.  22 (8), 623-636

    ISHIDATE, Jr., M., HARNOIS, M.C. AND SOFUNI, T. (1988) A comparative
    analysis of data on the clastogenicity of 951 chemical substances
    tested in mammalian cell cultures.   Mutat. Res.  195, 151-213

    LBI (1975) Litton Bionetics Incorporated Report PB-245 497 prepared
    for Food and Drug Administration.  Mutagenic evaluation of Compound
    FDA 71-18 Propylene glycol alginate. Dated 30 June 1975.  Submitted
    to WHO by Marinalg International, Paris, France

    MARTIN, G. (1986) Evaluation toxicologique et nutritionnelle des
    alginates: I.  Définition, structure, fabrication, proprietés et
    applications.   Sciences et Aliments 6, (no.4), 473-486

    MCNEELY, W.H. & SHEPHERD, V.M. (1966) Report to Kelco Co. Labs.

    MORGAN, F.C.(1959) As cited in Woodard (1959)

    MRCL (1951) Medical Research Council Laboratories.  Unpublished
    report.

    NEWELL, G.W. & MAXWELL, W.A. (1972) Unpublished Report from Stanford
    Research Institute, Menlo Park Co., submitted to DHEW/Public Health
    Service, U.S. FDA.

    NILSON, H.W. AND WAGNER, J.A. (1951) Feeding tests with some algin
    products.   Proc. Soc. Exp. Biol. Med. 76, 630-635.

    OUER, R.A.  et al. (1935)  J. Biol. Chem. 5, 108

    OUER, R.A. (1949) Sensitivity to Kelcoid.  Preliminary study.  Ann.
     Allergy 7, 681

    SHARRATT, M. & DEARN, P. (1972) An autoradiographic study of
    propylene glycol alginate in the mouse.   Food Cosm. Toxicol. 10,
    35-40

    SRI (1972) Stanford Research Institute Report PB-221 826 prepared
    for Food and Drug Administration.  Study of mutagenic effects of
    propylene glycol alginate (71-18). Dated June 1972.  Submitted to
    WHO by Marinalg International, Paris, France

    STEINER, A.B. & MCNEELY, W.H. (1951) Organic derivatives of alginic
    acid.  Ind. Eng. Chem. 43, 2073

    WOODARD, G. (1959) Unpublished Report.

    WOODARD RES. CORP. (1972) Unpublished Report on acute toxicity of
    PGA.


    See Also:
       Toxicological Abbreviations
       Propylene glycol alginate  (FAO Nutrition Meetings Report Series 46a)
       Propylene glycol alginate (WHO Food Additives Series 1)
       Propylene glycol alginate (WHO Food Additives Series 5)
       PROPYLENE GLYCOL ALGINATE (JECFA Evaluation)