Turmeric can be considered as both a flavouring agent and a food
    colour; curcumin is the main coloured component of turmeric.

         These substances were previously evaluated for an acceptable
    daily intake at the thirteenth, eighteenth, twenty-second, and
    twenty-sixth meetings of the Committee (Annex 1, references 19, 35,
    47, and 59). Toxicological monographs were prepared on each of these
    occasions (Annex 1, references 20, 36, 48, and 60).

         Temporary ADIs of 0-2.5 mg/kg b.w. for turmeric and 0-0.1 mg/kg
    b.w. for curcumin were allocated at the twenty-second meeting of the
    Committee, which were extended at the twenty-fourth meeting. New data
    on these substances were reviewed at the twenty-sixth meeting of the
    Committee, when the temporary ADIs were extended to 1986 pending the
    results of further studies.

         Since the previous evaluation, additional data have become
    available, which are summarized and discussed in the following
    monograph addendum. Data for turmeric oleoresin and for curcumin are
    presented and evaluated separately.



    Biochemical aspects

    Absorption, distribution and excretion

         In the short-term study on a test material containing 79%
    curcumin in Fischer 344 rats and B6C3F1 mice (see short-term studies
    below), it was reported that turmeric (presumably curcuminoid
    pigments) was detected in blood samples from both species at all dose
    levels and that blood plasma concentrations increased linearly in a
    dose-related manner over the dietary concentration range of 0.1-2.5%;
    at the higher dietary level of 5.0%, plasma levels tended to plateau.
    The data were claimed to be consistent with earlier reports (Wahlstrom
    & Blennow, 1978; Bolder et al, 1978) that the substance is poorly
    absorbed from the gut and is rapidly metabolized and excreted.
    However, this summary report is impossible to evaluate since there are
    obvious mistakes in the data supplied and the basis of calculations of
    percentage of the dose in blood is unclear (Lilja, 1984).

    Toxicological studies

    Acute toxicitya

    Animal      Route      LD50 (g/kg b.w.)      Reference

    Mouse       Oral       > 10                  Lilja et al., 1983
    Rat         Oral       > 10                  Lilja et al., 1983

    a    The test material was estimated to contain about 79% curcumin.

    Short-term studies


         Groups of 10 male and 10 female B6C3F1 mice, aged 8-9 weeks,
    received curcumin in the diet at concentrations of 0, 0.1, 0.5, 1.0,
    2.5, or 5.0% for 13 weeks. The test material contained approximately
    79% curcumin. Food intake and body-weight gain were recorded weekly.
    Urinalysis was performed eight days prior to termination and blood was
    collected for haematology and clinical chemical analyses at the end of
    the study. Gross necropsies were performed on all animals and detailed
    histological examinations were carried out on the control and 5% dose
    groups only. No significant differences attributable to treatment were
    observed in body-weight gain, mortality, or histopathology, but a
    dose-related increase in liver weight occurred in both sexes.

    Decreases were observed in lung weight, which achieved statistical
    significance in males of the two highest-dose groups only, in thymus
    weight, significant only at the 2.5% level, and in kidney weight,
    significant in females of the top-dose group only. Haemetological
    changes observed were not dose-related and the values were within
    normal ranges. Clinical chemistry analyses revealed dose-related
    increases in cholinesterase and phosphorus, which were significant at
    the 1% and higher dose levels in males and at the top two dose levels
    (cholinesterase) or top-dose group only (phosphorus) in females. A
    dose-related decrease in creatinine levels occurred in females at all
    but the lowest dose level and in males at the top three dose levels.
    The no-effect level with respect to gross and microscopic pathological
    changes was 5% of the diet, equal to a time-weighted average of 9280
    and 7700 mg/kg b.w./day in females and males, respectively
    (Lilja et al., 1983).


         A 13-week study was carried out in F344 rats using a similar
    protocol and at the same dose levels as described for mice above. No
    significant differences due to treatment were observed in body-weight
    gain, mortality, or histopathology. There was a dose-related increase
    in liver weight in both sexes; in females there was also a
    treatment-related decrease in heart and lung weights. Haematological
    examination showed a dose-related increase in polymorphonuclear
    lymphocytes at the 2.5 and 5% dose levels in males while in females
    there was a small increase only at the 5% level. In females,
    erythrocyte counts tended to be lower in a treatment-related but not a
    consistent dose-related manner; other haemetological changes were not
    dose-related. Clinical chemistry analyses in males revealed a number
    of changes at the mid- to high-dose levels; SGPT, OCT, total protein,
    globulin, urea nitrogen, creatinine, and total bilirubin were lower
    while the albumin/globulin ratio, direct bilirubin, and chloride
    tended to be higher than in controls. Decreased SGOT and LDH were
    observed only at the highest-dose level. In females, decreases were
    observed in LDH, creatinine, total bilirubin, pH, bicarbonate, and
    total CO2, while phosphorus was increased at the two higher-dose
    levels. Urinalysis of male rats indicated that there was a
    treatment-related increase in casts and an increase in red blood cells
    at the top two dose levels. Urine of females showed little or no
    treatment-related change except for increased uric acid crystals at
    all dose levels and a slight increase in red and white blood cells at
    the top-dose levels.

         The no-effect level with respect to gross and microscopic
    pathological changes was 5% of the diet, equal to a time-weighted
    average of 2760 and 2587 mg/kg b.w./day in females and males,
    respectively (Lilja et al., 1983).


         The short-term studies in rats and mice on test material
    containing approximately 79% curcumin indicated a low short-term
    toxicity, although evidence of minimal hepatotoxicity and
    nephrotoxicity was seen in the high-dose acute toxicity study by

         It is understood that the long-term carcinogenicity study
    required at the twenty-sixth meeting (Annex 1, reference 59) on
    curcumin was nearing completion. No details were available regarding
    the required multigeneration reproduction/teratology study on
    curcumin. This evaluation is based on earlier studies pending the
    results of the long-term carcinogenicity study.


    Estimate of temporary acceptable daily intake for man

    0-0.1 mg/kg b.w.

    Further work or information

    Required (by 1989)

         1. Adequate long-term carcinogenicity study in a rodent species.

         2. Multigeneration reproduction/teratology study.


    Holder, G., Plummer, J., & Ryan, A. (1978). The metabolism and
         excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl-
         1,6-heptadiene-3,5-dione) in the rat. Xenobiotica,
         8, 761-768.

    Lilja, H.S., Hagopian, M., Esber, H.J., Fleischman, R.W.,
         Russfield, A.B., & Tiedemann, K.M. (1983). Report on the
         subchronic toxicity by dosed feed of turmeric oleoresin (C60015)
         in Fischer 344 rats and B6C3F1 mice. EGG Mason Research
         Institute, Report No. MRI-NTP 11-83-22. Submitted to WHO by the
         National Institutes of Health, Research Triangle Park, NC, USA.

    Lilja, H.S. (1984). Final report amendment. EG&G Mason Research
         Institute, Report No. MRI-NTP 11-83-22. Submitted to WHO by the
         National Institutes of Health, Research Triangle Park, NC, USA.

    Wahlstrom, B. & Blennow, G. (1978). A study on the fate of curcumin in
         the rat. Acta Pharmacol. Toxicol., 43, 86-92.



    Toxicological studies

    Special studies on mutagenicity

         Turmeric oleoresin was not mutagenic in the Ames assay using
    Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, with
    or without metabolic activation by S-9 preparations from Aroclor
    1254-induced rats or Syrian hamsters (Spalding, 1983).

    Short-term studies


         Turmeric oleoresin (containing 17.5% curcumin) was fed for
    102-109 days to groups of 4 male and 4 female pigs (Danish
    Landrace-Yorkshire and Danish Landrace) at dietary levels providing
    intakes of 60, 296, or 1551 mg/kg b.w./day; 6 male and 6 female pigs
    served as controls. The highest-dose group of both sexes showed a
    reduction in body-weight gain and food conversion efficiency.
    Dose-related increases in the weights of the liver and thyroid were
    observed, achieving statistical significance in all treatment groups
    of females and the top two dose groups of males. Histologically, all
    animals (both sexes) in the top-dose group and all but one in the
    intermediate-dose group showed peribiliar infiltration with
    lymphocytes; in some animals lymphocytes were also present in the
    smaller bile ducts, in the interstices, and in the periportal
    parenchyma. In the two higher-dose groups epithelial changes were
    observed in the terminal part of the kidney collecting tubules, in the
    papillae, and in the urinary bladder; the changes took the form of
    increased epithelial cell size, less dense cytoplasm, and nuclei
    changed from a basal to intermediary position in the cells. An
    increased number of cell layers in the bladder epithelium was also
    observed. Hyperplasia of thyroid follicular calls was seen in the top
    two dose groups and paralleled the increase in organ weight. A clear
    no-effect level could not be established with respect to increased
    thyroid weight, and clear morphological changes were seen in the two
    highest-dose groups (Bille et al., 1985).


         The short-term study in pigs on turmeric oleoresin (containing
    17.5% curcumin) was in response to the previous requirement for such a
    study in a non-rodent species. Histopathological changes were observed
    in the liver, kidney, bladder, and thyroid of animals in the two
    highest-dose groups, including hyperplasia of thyroid follicular
    cells, and increased thyroid weights occurred at the lowest dose

    (60 mg/kg b.w./day) tested. It was not possible to establish a
    no-effect level in this study and comparison with earlier studies
    suggests that the pig is more sensitive than rodents to the effects of
    turmeric oleoresin.


    Estimate of temporary acceptable daily intake for man

         0-0.3 mg/kg b.w. (based on minimal changes in the short-term
    study in pigs).

    Further work or information

    Required (by 1989)

         Results of a short-term study in the pig or another non-rodent
    species. If this study is performed in a species other than the pig,
    the design should enable a comparison to be made of the sensitivity of
    the test species with that observed in the short-term pig study. A
    clear no-effect level should be established.


    Bille, N., Larsen, J.C., Hansen, E.V., & Wurtzen, G. (1985).
         Subchronic oral toxicity of turmeric oleoresin in pigs.
         Fd. Chem. Toxicol., 23, 967-973.

    Spalding, J.W. (1983). Genetic toxicity report on turmeric oleoresin
         (8024-37-1). Unpublished report submitted to WHO by the National
         Institutes of Health, Research Triangle Park, NC, USA.

    See Also:
       Toxicological Abbreviations