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    CARNAUBA WAX

    First draft prepared by
    Dr Karen B. Ekelman and Dr Hui-Chen Chang
    US Federal Administration
    Washington DC, USA

    1.  EXPLANATION

         Carnauba wax has not been evaluated previously by the Joint
    FAO/WHO Expert Committee on Food Additives. Carnauba wax is obtained
    from the leaves and buds of the Brazilian wax palm,  Copernica
     cerifera. The wax is hard, brittle, sparingly soluble in cold
    organic solvents and insoluble in water.

    2.  BIOLOGICAL DATA

    2.1  Biochemical aspects

         No information available.

    2.2  Toxicological studies

    2.2.1  Acute toxicity studies

         No information available.

    2.2.2  Short-term studies

    2.2.2.1  Rats

         Three experiments have been conducted. In the first experiment,
    groups of 15 male and 15 female Wistar rats were fed diets
    containing 0 (control group), 1, 5, or 10% carnauba wax or 10%
    cellulose powder for 13 weeks. The rats fed diets containing
    cellulose powder acted as a control group for possible effects due
    to the replacement of a significant proportion of the diet by a
    non-nutrient test material. In the second and third experiments,
    groups of five rats of each sex were fed diets containing 1%
    carnauba wax then 10% carnauba wax or 10% cellulose powder for 2 and
    6 weeks, respectively. Food consumption and body weights were
    recorded weekly only in the 13-week study. Haematological, serum,
    and urinalysis and gross and microscopic examinations of tissues
    were used to evaluate the toxicity of carnauba wax.

         Results from the 13-week study indicated that rats given 10%
    carnauba wax consumed more food than the controls, but showed no
    differences in body weight. Similar results were also seen in the
    rats given 10% cellulose powder in the diet. The calculated mean
    intakes of carnauba wax were 0, 800, 4200 and 8800 mg/kg bw/day for
    males and 0, 900, 4600 and 10 200 mg/kg bw/day for females.

         Blood samples were collected at weeks 2, 6 and 13 for
    haematological examination and serum analyses; results of these
    analyses were similar for treated and control animals. Urinalysis at
    weeks 2, 6 and 13 of the study did not show any treatment-related
    changes. Organ weights (brain, pituitary, thyroid, heart, liver,
    spleen, kidneys, adrenal glands, gonads, stomach, small intestine
    and caecum) showed no compound-related changes, nor were there any
    dose-related histological changes (Rowland, 1982).

    2.2.2.2  Dogs

         Four groups of 6 male and 6 female Beagle dogs were exposed to
    0 (control), 0.1, 0.3, or 1% carnauba wax in their diets for 28
    weeks. Food consumption, body weights and behavioural effects were

    recorded weekly. Blood and urinary samples were collected at weeks
    11 and 26. Organs were weighed (brain, pituitary gland, thyroid
    gland, heart, liver, spleen, kidneys, and adrenal glands) and gross
    and microscopic examinations of tissues were performed at the end of
    study.

         No significant differences in body weights nor food consumption
    were noted between treatment and control groups of animals. Data
    from analyses of blood, urine and organ weights did not show any
    treatment-related effects in dogs consuming carnauba wax. The only
    significant (p <0.05) clinical observation at 26 weeks was higher
    free fatty acid levels in male dogs at all dietary levels of
    carnauba wax as compared to controls. However, free fatty acid
    levels in all male dogs fed carnauba wax were well within the normal
    range for Beagle dogs (200-800 µM/l) whereas values for control dogs
    were unusually low (138 ± 38 µM/l). Ophthalmic, gross and
    histopathologic examinations revealed no significant
    treatment-related effects for up to 1% carnauba wax in the diet
    (Parent, 1983a).

    2.2.3  Long-term/carcinogenicity studies

         No information available.

    2.2.4  Reproduction studies

         Four groups of 25 female (F0) and 25 male Wistar rats were
    administered 0, 0.1, 0.3, or 1% carnauba wax in the diet for 4 weeks
    prior to mating and throughout the remainder of the study, including
    gestation and lactation. Each (F1) pup was supplied with the same
    diet as its dam through weaning and for an additional 13 weeks. Food
    consumption and body weights were recorded weekly for the F0
    generation (except during mating) and the F1 generation. F0
    females were weighed on days 0, 6, 11, 15 and 20 of gestation. Total
    litter weights were measured at birth and at 4, 14 and 21 days after
    birth. The number of pregnant females, number of pups born alive or
    dead, and survival of the progeny were recorded. Ophthalmic
    examinations were performed on the F1 animals at the time of
    weaning and at the end of the 13-week study. Haematological and
    clinical chemical measurements were performed on F1-generation
    animals at weaning and at 6 and 13 weeks thereafter. Complete gross
    necropsies were performed an all F0 animals, F1 animals that
    were killed after weaning, and F1 animals used for the
    post-weaning 13-week feeding study. Organs (adrenal glands,
    epididymides, heart, liver, kidneys, ovaries, spleen, testes,
    thyroid with parathyroid glands, and uterus) from animals used in
    the post-weaning 13-week feeding study were weighed, and
    histopathological examination of the weighed organs and other organs
    (brain, eyes, large and small intestine, lungs, lymph nodes,
    pancreas, pituitary gland, sciatic nerve, seminal vesicles, skeletal

    muscle, skin, spinal cord, sternum and marrow, stomach, urinary
    bladder, and grossly abnormal lesions) for animals in control and
    high-dose groups was performed. For animals in the low and
    middle-dose groups, only grossly abnormal tissues were examined
    microscopically.

         No effects on reproduction parameters (fertility indices,
    gestation indices, viability indices, lactation indices and pup
    weights) were observed after feeding carnauba wax to pregnant
    F0-generation female rats at levels up to 1% of the diet. Although
    scattered significant differences (p <0.05) between groups in body
    weights and food consumption of male and female rats in both the
    F0 and F1 generations were noted (data not shown in report), the
    magnitude of the changes was small and did not show a clear dose
    relationship indicative of a compound-related effect. This study
    reported that mean intake of carnauba wax calculated on the basis of
    food consumption during the 13 weeks of the study was 0.08, 0.25,
    and 0.81 g/kg bw/day for males and 0.09, 0.27, and 0.67 g/kg bw/day
    for females treated at levels of 0.1, 0.3, and 1.0% carnauba wax,
    respectively.

         A statistically significant increase (p <0.05) in haematocrit
    of female rats fed diets containing 0.1% and 1% carnauba wax was
    noted at end of study, but was not observed in animals fed 0.3%
    carnauba wax. Blood urea nitrogen levels were significantly elevated
    (p <0.05) in males fed diets containing 0.1 and 1% carnauba wax for
    6 weeks and in males fed diets containing 1% carnauba wax for 13
    weeks. Although serum glutamate-pyruvate transaminase decreased and
    chloride increased in male rats fed 0.3 and 1% carnauba for 13
    weeks, the values were reported to be within the normal
    physiological ranges for Wistar rats. A decrease in serum free fatty
    acids was seen in male and female rats fed carnauba wax at dietary
    levels of 0.3% and 1% at week 13. Those haematology and clinical
    chemistry changes did not appear to be related to consumption of
    carnauba wax.

         There were no treatment-related differences in histological,
    ophthalmic and gross pathology findings in either F0 or F1
    animals at any dietary level of carnauba wax used in this study
    (Parent  et al., 1983b).

    2.2.5  Special studies on mutagenicity

         Results of mutagenicity studies on carnauba wax are summarized
    in Table 1.


        Table 1. Results of Mutagenic Studies on Carnauba Wax
                                                                                                                

    Test System         Test Object           Concentration of      Results         References
                                               Carnauba Wax
                                                                                                                

    Ames test1          S. typhimurium        3.3-1000 µg in        Negative        Mortelmans and Griffin,
                        TA1537, TA1538,       plate tests                           1981
                        TA98

    Ames test1          S. typhimurium        0.01-0.5% in          Negative        Mortelmans, and Griffin
                        TA1537, TA1538,       suspension tests                      1981
                        TA98

    Ames test1          S. typhimurium        0.1-2.5% in           Negative        Mortelmans, and Griffin
                        TA1537, TA1538,       suspension tests                      1981
                        TA98

    Gene mutation2      S. typhimurium        0.01% in plate        Negative        Litton Bionetics,
                        TA1535, TA1537,       tests                                 Inc., 1975
                        TA1538

    Gene mutation2      S. typhimurium        0.005 and 0.01% in    Inconsistent    Litton Bionetics,
                        TA1535, TA1537,       suspension tests      changes3        Inc., 1975
                        TA1538

    Gene mutation2      S. cerevisiae         0.3 and 1.75% in      Negative        Litton Bionetics,
                        D4                    suspension tests                      Inc., 1975
                                                                                                                

    1    The Ames/ Salmonella assays in the presence and absence of an Aroclor 1254-stimulated,
         rat-liver homogenate metabolic activation system, were used in this study.
    2    A series of  in vitro microbial assays with and without metabolic activation were used.
         In the activation assays, the tissue homogenate of liver, lung and testes were
         prepared from either mouse, rat or monkey.
    3    The results from non-activation suspension tests were negative. The results from
         activation suspension tests showed scattered increased mutation responses in the
         presence of rat-liver or testes homogenate with strain TA1537, and in the
         presence of monkey-lung homogenate with TA1538.
    

    2.2.6  Special studies on teratogenicity

         Four groups of Wistar rats, each consisting of 25 females, were
    mated to test for teratogenic effects; they were fed 0 (control),
    0.1, 0.3 or 1% carnauba wax in the diet for two weeks before mating
    and throughout gestation. Body weights of pregnant dams were
    recorded on days 0, 6, 11, 15, and 20 of gestation. On day 20 of
    gestation, pregnant females were killed, caesarian sections were
    performed, and gross pathological changes were noted. The uterine
    contents were examined and the following litter reproduction data
    were recorded: number of corpora lutea, implantation sites,
    resorption sites, live and dead fetuses; gross malformations; and
    body weights of live fetuses. One-half of fetuses were examined for
    signs of visceral pathological changes and the other half were
    examined for signs of skeletal abnormalities.

         Results from this study indicated that there were no
    significant changes in body weights of pregnant dams during
    gestation; no significant differences in reproduction data among
    test groups; and no dose-related effects of carnauba wax on skeletal
    or soft tissue development in fetuses (Food and Drug Research
    Laboratories, Inc., 1977).

    2.3  Observations in man

         No information available.

    3.  COMMENTS

         Short-term feeding studies of carnauba wax at 10% in the diet
    of rats showed no significant compound-related toxic effects. In a
    28-week study with beagle dogs in which carnauba wax was fed at
    levels of 0/1, 0/3, and 1% in the diet, no compound-related toxic
    effects were identified.

         No adverse effects were observed in fetuses in a teratogenicity
    study in rats following dietary exposure 0/1, 0/3, and 1% carnauba
    wax during gestation.

         A reproduction study combined with a 13-week oral toxicity
    study with F1 animals was conducted in Wistar rats. During both
    phases of the study, animals (parents and offspring) were fed diets
    containing 0/1, 0/3, or 1% carnauba wax. No adverse effects
    associated with the consumption of carnauba wax at levels up to 1%
    of the diet (equal to 700 mg/kg bw/day for female rats) were
    observed in this experiment.

         Although the results of mutagenicity studies were largely
    negative, scattered positive responses with  S. typhimurium strains
    TA1537 and TA1538 were observed in the presence of metabolic
    activation.

    4.  EVALUATION

         The Committee allocated an ADI of 0-7 mg/kg bw for carnauba
    wax.

    5.  REFERENCES

    FASEB (1975) Evaluation of the health aspects of carnauba wax as a
    food ingredient.  SCOGS-47.

    FOOD AND DRUG RESEARCH LABORATORIES, INC. (1977) Evaluation of the
    effects of carnauba wax in FDRL/Wistar derived rats after dietary
    exposure through one full generation. Unpublished report of July 8,
    1977 submitted to Brazilian Embassy, Washington, D.C.

    LITTON BIONETICS INC. (1975) Mutagenic evaluation of compound
    MX8015869, carnauba wax (73-48). Unpublished report of April 15,
    1975, submitted to Food and Drug Administration, Rockville, MD, 33
    pp.

    MORTELMANS, K.E. & GRIFFIN, ANN. F. (1981) Microbial mutagenesis
    testing of substances compound F73-048: carnauba wax, yellow.
    Unpublished SRI Report LSU-6909 from Frank B. Ross & Co. Submitted
    to Food and Drug Administration by Frank B. Ross & Co. Report
    (LSU-6909), 19 pp.

    PARENT, R.A., COX, G.E., BABISH, J.G., GALLO, M.A., HESS, F.G. &
    BECCI, P.J. (1983a) Subchronic feeding study of carnauba wax in
    beagle dogs.  Fd. Chem. Toxicol., 21(1): 85-87.

    PARENT, R.A., RE, T.A., BABISH, J.G., COX, G.E., VOSS, K.A. & BECCI,
    P.J. (1983b) Reproduction and subchronic feeding study of carnauba
    wax in rats.  Fd. Chem. Toxicol., 21(1): 89-93.

    ROWLAND, I.R., BUTTERWORTH, K.R., GAUNT, I.F., GRASSO, P. &
    GANGOLLI, S.D. (1982) Short-term toxicity study of carnauba wax in
    rats.  Fd. Chem. Toxicol., 20: 467-471.


    See Also:
       Toxicological Abbreviations
       CARNAUBA WAX (JECFA Evaluation)