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    SHELLAC

    First draft prepared by
    Dr K.B. Ekelman and Dr D. Benz
    US Food and Drug Administration
    Washington DC, USA

    1.  EXPLANATION

         Shellac has not been previously evaluated by the Committee. It
    has a long history of use in food coatings and there are no reports
    attributing adverse effects to such uses.

    2.  BIOLOGICAL DATA

    2.1  Biochemical aspects

    2.1.1  Absorption, distribution, and excretion

         Relative dissolution rates of shellac- and cellulose-acetate
    phthalate-coated prednisolone tablets were studied in humans in a
    double-blind, crossover clinical trial. Subjects were six volunteers
    (5 males, 1 female; mean age 26 years) who were not receiving any
    other medication at the time of the study. Plasma prednisolone
    concentration was significantly lower after administration of
    shellac-coated tablets than after administration of cellulose
    acetate phthalate-coated tablets, and considerable inter-individual
    variation was noted in plasma prednisolone levels after
    administration of shellac-coated tablets (Lee  et al., 1979).

         Information on bioavailability, distribution and rate of
    excretion of shellac are not available.

    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 acute oral toxicity of four types of food-grade shellac was
    determined in rats. Groups of ten rats were administered a single
    gavage dose (5 g/kg) of one of four types of shellac in aqueous
    suspension. No deaths were recorded (Levenstein, 1980). Table 1
    summarizes the results of this study.

        Table 1: Acute toxicity of shellac (Leberco Laboratories Data Summary)
                                                                                  

    Type of test material                             No. Fed/No. Dead
                                                                                  

    Regular Bleached Bone-Dry Shellac                     10/0

    Refined Wax-Free Bone-Dry Bleached Shellac            10/0

    Orange with Wax Shellac                               10/0

    Orange Wax Free Shellac                               10/0
                                                                                  

    

         The report did not supply information on the identity of the
    rat strain used in this study.

    2.2.2  Short-term studies

         In a 90-day rat feeding study, 42 female SIV 50 rats (average
    weight, 76 g) were divided into three groups. Groups 1 and 2 were
    fed diets containing 2% shellac (each group was fed a different
    brand of food-grade shellac) for 90 days; Group 3 rats served as
    controls. The average feed consumption was 13.2 g/d, and average
    weight gains for animals in Groups 1 and 2 (127 ± 11.4 g and 128.6 ±
    12.7 g, respectively) did not differ significantly from the average
    weight gain for animals in Group 3 (123.7 ± 9.9 g) The investigator
    reported that shellac had no effect on the appetite of test animals,
    and no residues of shellac were detected in the test animals'
    faeces. At the end of the study four rats from each group were
    examined histologically (liver, duodenum, ileum, caecum, colon, and
    kidneys). Although animals fed shellac tended to have enlarged caeca
    and swelling in the proximal region of the colon, gross examination
    revealed no pathological changes in the intestinal tract, liver, nor
    kidneys. Colons of control rats exhibited less intestinal
    eosinophilia than those of shellac-fed rats and less oedema of the
    lamina propria was detected in the caeca of control and Group 2 rats
    than in Group 1 rats. Although this study did not identify
    pathological changes associated with the consumption of shellac,
    results were confounded by the failure of growth in both
    experimental and control animals during the latter phase of the
    study (Buchloch, 1979).

    2.2.3  Long-term/carcinogenicity studies

         No information available.

    2.2.4  Reproduction/teratogenicity studies

         Regular bleached shellac was evaluated in a 90-day toxicity
    study with an  in utero exposure phase. Twenty-five Sprague-Dawley
    rats per sex (F0) were fed commercial diets containing 0
    (control), 1000, 3000, and 10 000 ppm shellac for 28 consecutive
    days. Animals within groups were mated after this period, and
    females were allowed to deliver and wean a single litter. On day 4
    of lactation, litters were culled to 5 male and 5 female rats, if
    possible. Twenty-five weaned F1 animals per sex from each group
    were randomly selected for the 90-day study, and were fed the same
    diets as their parents had consumed. Animals were killed after 11
    weeks (F0 males) or 13 weeks (F0 females, F1 animals) of
    consumption of shellac-containing or control diets. The following
    assessments were made for test and control groups of rats:
    mortality; external physical, behavioural and developmental signs of
    toxicity; body weight; feed consumption; reproduction and
    developmental indices; haematology; clinical chemistry; urine
    analysis; gross necropsy; and histopathological examination. There
    was no evidence of treatment-related toxicological effects in
    shellac-fed F0 and F1 animals (FDRL, 1984).

    2.2.8  Special studies on mutagenicity

         Food grade regular bleached shellac was evaluated for
    mutagenicity in a series of  in vitro microbial assays.

         Mutagenicity evaluation of shellac using the Ames
     Salmonella/microsome plate test was performed on concentrations
    ranging from 1 to 10 000 œg/plate shellac in corn oil. These
     in vitro microbial plate assays were performed in the absence and
    in the presence of a metabolic activation system (S9 fraction from
    Aroclor-induced rats). The negative control for both activation and
    non-activation assays consisted of incubation of the strains with
    corn oil alone. The positive control, 2-anthramine in DMSO at a
    concentration of 2.5 µg/plate, was used in the activation assays
    with all strains. No toxicity was observed in any of the indicator
    strains used. No increase in the number of revertants was observed
    in any strain either in the presence or in the absence of metabolic
    activation. Results of these studies are summarized in Table 2.

        Table 2: Summary of mutagenicity studies with shellac
                                                                                  

    Test material       System             Strain      Results      Reference
                                                                                  

    Food Grade          Salmonella         TA-1535     negative     Jagannath &
    regular bleached    typhimurium        TA-1537                  Myln, 1981
    Shellac                                TA-1538
                                           TA-98
                                           TA-100

    Shellac Wax         Salmonella         TA-1535     negative     Brusick, 1975
                        typhimurium        TA-1537
                                           TA-1538

    Shellac Wax         Saccharomyces      D4          negative     Brusick, 1975
                        cerevisiae
                                                                                  
    
    2.2.9  Special studies on immune responses

         No information available.

    2.3  Observations in humans

    2.3.1  Respiratory studies

         The possible association between the inhalation of shellac in
    hair sprays and respiratory disease has been studied. An acute
    respiratory toxicity study was conducted using an unreported number
    of women volunteers (Draize  et al., 1959). Of the six hair spray
    formulations tested in this study, one contained shellac. Exposure
    in a test cubicle to each spray lasted 10 or 30 seconds with an
    additional 5 min in the cubicle with the sprayed atmosphere. This
    exposure to shellac was reported to be insufficient to produce
    adverse effects. Non-volatile components of the sample atmosphere
    were determined and considered to be negligible. No data on the
    subjects' age, weight, and physical health were given. Exposures for
    this study are summarized in Table 3, below.

        Table 3: Human exposure to shellac type hair spray
                                                                        

      Spray Released                 Nonvolatile Spray
                                                                        

    sec             g            in air, g      inspired, g

     10            8.8            0.0024          0.00016

     30           22.5            0.0038          0.0002
                                                                        
    
         A paper by Gelfand (1963) documents allergies (particularly
    bronchial asthma and allergic skin reactions) reportedly caused by
    exposure to chemical compounds in the rubber, lacquer, shellac, and
    beauty industries through reports of patients exposed to the
    compounds as customers or workers in these industries. The author
    suggested that respiratory allergies reported to be associated with
    inhalation of shellac were not due to shellac but to other solvents.

    2.3.2  Oral toxicity

         No information on human oral dosing was available.

    2.3.3  Long-term studies

         Little is known about the effects of long-term exposure to
    shellac on humans. A forensic autopsy of a 55-year old male cabinet
    maker found a hardened mass of shellac (bezoar) in his stomach
    (Janica, 1983). Cause of death was reported to be from trauma to the
    skull caused by a fall. How the shellac was ingested remains
    unclear.

    3.  COMMENTS

         As evaluated by mirobial assays, shellac is not mutagenic. In a
    90-day study, female rats fed diets containing shellac showed caecal
    enlargement and swelling in the proximal region of the colon. There
    were no hisopathological changes associated with the consumption of
    shellac, although the results were confounded by the failure of both
    experimental and control animals to grow during the latter part of
    the study.

         A recent 90-day study (including an  in utero exposure phase)
    produced no evidence of treatment-related toxic or pathological
    effects in F0 or F1 rats fed diets containing up to 1% shellac
    (equal to 660 mg/kg bw/day for female rats).

    4.  EVALUATION

         The Committee concluded that the present functional uses of
    shellac (as a coating, glazing and surface-finishing agent applied
    externally to food) were of no toxicological concern.

    5.  REFERENCES

    BRUSICK, D. (1975). Mutagenic evaluation of compound PM 90000593
    shellac wax (73-51). Unpublished report from Litton Bionetics, Inc.,
    Kensington, MD, USA. Submitted to Food and Drug Administration,
    Rockville, MD, USA.

    BUCHLOCH, G. (1979). Anatomical-histological examination: 42 rats
    fed with shellac. Unpublished report from the American Bleached
    Shellac Manufacturers Association, Inc., New York, USA. Submitted to
    the Federation of American Societies for Experimental Biology,
    Bethesda, MD, USA.

    COSMETIC INGREDIENT REVIEW (CIR). (1986). Final report on the safety
    assessment of shellac.  J. Amer. Coll. Tox., 5: 309-327.

    DRAIZE, J.H., NELSON, A.A., NEWBURGER, S.H., & KELLEY, E.A. (1959).
    Non-toxicity of aerosol hair sprays.  Drug & Cosmetic Ind., 84:
    592-593, 644, 652.

    FDRL (1984). Ninety-day (in utero) dietary toxicity study of regular
    bleached shellac in Sprague-Dawley rats. FDRL study No. 7455. Report
    from Food and Drug Research Laboratories, Waverly, New York, USA.
    Submitted to WHO by the American Bleached Shellac Manufacturers
    Association, Inc., New York, NY, USA.

    FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY (FASEB).
    (1981). Evaluation of the health aspects of Shellac and Shellac Wax
    as food ingredients. Final Report for FDA.
    Publication No. PB82-160383.

    GELFAND, H.H. (1963). Respiratory allergy due to chemical compounds
    encountered in the rubber, lacquer, shellac and beauty culture
    industries.  J. Allergy, 38: 374-381.

    JAGANNATH, D.R. & MYLN, B.C. (1981). Mutagenicity evaluation of
    regular bleached food grade shellac in the Ames
     Salmonella/microsome plate test. Unpublished report from the
    Litton Bionetics, Inc. Kensington, MD, USA submitted to Federation
    of American Societies for Experimental Biology, Bethesda, MD, USA by
    American Bleached Shellac Manufactures Association, Inc., New York,
    NY, USA.

    JANICA, J. (1983). Shellac bezoar of the stomach.  Wiad. Lek., 36:
    881-883.

    LEE, D.A.H., TAYLOR, G.M., WALKER, J.G. & JAMES, V.H.T. (1979). The
    effect of food and tablet formulation on plasma prednisolone levels
    following administration of enteric-coated tablets.  Br. J. Clin.
     Pharmac., 7: 523-528.

    LEVENSTEIN, I. (1980). Acute oral toxicity study on five types of
    food grade Shellacs in rats. Unpublished report from Leberco
    Laboratories submitted to Food and Drug Administration, Rockville,
    MD, USA.

    ROGERS, R. (1978). Monograph on shellac. FDA Publication No. PB 287
    765.


    See Also:
       Toxicological Abbreviations