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Toxicity Effects

CAS Registry Number: 458-37-7

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 2.

Names 1

  • 1,7-Bis(4-Hydroxy-3-Methoxyphenyl)Hepta-1,6-Diene-3,5-Dione
  • C.I. Natural Yellow 3
  • CURC
  • Curcuma
  • Curcumin
  • Diferuloylmethane
  • Indian Saffron
  • Merita Earth
  • Souchet
  • Yellow Ginger
  • Yellow Root

Human Toxicity Excerpts

  • ALTERNATIVE and IN VITRO TESTS: ... Curcumin, diferuloyl methane, the yellow pigment component of the curry spice turmeric (Curcuma longa), has immense biological effects and has recently drawn considerable attention. Curcumin has antibacterial, antiviral, antiinflammatory, and anticancer properties. It has shown a lack of toxicity in animals and human clinical trials. Yet, its effect on reproduction has not been examined. The present study was conducted to examine if curcumin affects sperm function in vitro and fertility in vivo. Sperm (human and murine) were collected and incubated with curcumin to examine the effect on motility, capacitation/acrosome reaction, and in vitro fertilization. The effect on in vivo fertility using the mouse model was also examined. Incubation of sperm with curcumin caused a concentration-dependent decrease in sperm forward motility, capacitation/acrosome reaction, and murine fertilization in vitro. At higher concentrations, there was a complete block of sperm motility and function within 5-15 min. Administration of curcumin, especially intravaginally, caused a significant (P<0.001) reduction in fertility. The antifertility effect of curcumin was reversible. /This study reports/ the inhibitory effect of curcumin on sperm function, fertilization, and fertility. The findings suggest that curcumin may constitute a double-edged sword to block conception, infection, and cancer, thus providing an ideal contraceptive.[Naz RK; Mol Reprod Dev 78 (2): 116-23 (2011)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: A novel polymeric amphiphile, mPEG-PA, was synthesized with methoxy poly(ethylene glycol) (mPEG) as the hydrophilic and palmitic acid (PA) as the hydrophobic segment. The conjugate prepared in a single-step reaction showed minimal toxicity on HeLa cells. (1)H nuclear magnetic resonance imaging and Fourier transform infrared spectroscopy revealed that the conjugation was through an ester linkage, which is biodegradable. Enzymes having esterase activity, such as lipase, can degrade the conjugate easily, as observed by in vitro studies. mPEG-PA conjugate undergoes self-assembly in an aqueous environment, as evidenced by fluorescence spectroscopic studies with pyrene as a probe. The mPEG-PA conjugate formed micelles in the aqueous solution with critical micelle concentration of 0.12 g/L. Atomic force microscopy and dynamic light scattering studies showed that the micelles were spherical in shape, with a mean diameter of 41.43 nm. The utility of mPEG-PA to entrap the potent chemopreventive agent curcumin in the core of nanocarrier was investigated. The encapsulation of a highly hydrophobic compound like curcumin in the nanocarrier makes the drug readily soluble in an aqueous system, which can increase the ease of dosing and makes intravenous dosing possible. Drug-loaded micelle nanoparticles showed good stability in physiological condition (pH 7.4), in simulated gastric fluid (pH 1.2) and in simulated intestinal fluid (pH 6.8). This micellar formulation can be used as an enzyme-triggered drug release carrier, as suggested by in vitro enzyme-catalyzed drug release using pure lipase and HeLa cell lysate. The IC(50) of free curcumin and encapsulated curcumin was found to be 14.32 and 15.58 uM, respectively. /Molecular carrier system/[Sahu A et al; Acta Biomater 4 (6): 1752-61 (2008)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: Amphiphilic polymers for dual drug delivery have been a focus of research in recent years. /Investigators/ have previously developed and characterized Lauroyl sulphated chitosan (LSCS). Here biological characterizations like mucoadhesion, cytotoxicity, calcium binding, tight junction opening and enzymatic degradation studies were performed to understand its applicability. In vitro drug release properties of both hydrophilic insulin and hydrophobic curcumin were carried out. The biological activity and stability of released insulin were also studied. The stability studies of encapsulated curcumin and uptake studies have also been carried out. LSCS showed strong mucoadhesion and 100% of non-toxicity. LSCS could transiently open tight junctions between Caco-2 cells and thus increase the paracellular permeability. LSCS enhanced calcium binding properties and decreased enzymatic degradation rate retaining insulin activity. LSCS could protect curcumin from photodegradation and could also enter into the cells. From release studies, LSCS was found to be a suitable candidate for both drugs. /Lauroyl sulphated chitosan encapsulated curcumin/[Shelma R, Sharma CP; Colloids Surf B Biointerfaces 88 (2): 722-8 (2011)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: Curcumin is a naturally occurring compound which is known to induce heme oxygenase 1 (HO-1), although the underlying mechanism has not been fully elucidated. This study investigates in detail the mechanism of HO-1 induction by curcumin in human hepatoma cells. There was increasing toxicity of curcumin at concentrations higher than 10 uM...[McNally SJ et al; Int J Mol Med 19 (1): 165-72 (2007)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: Curcumin, a natural polyphenolic pigment present in the spice turmeric (Curcuma longa), is known to possess a pleiotropic activity such as antioxidant, anti-inflammatory, and anti-amyloid-beta activities. However, these benefits of curcumin are limited by its poor aqueous solubility and oral bioavailability. In the present study, a polymer-based nanoparticle approach has been utilized to deliver drugs to neuronal cells. Curcumin was encapsulated in biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation (Nps-Cur). Dynamic laser light scattering and transmission electronic microscopy analysis indicated a particle diameter ranging from 80 to 120 nm. The entrapment efficiency was 31% with 15% drug-loading. In vitro release kinetics of curcumin from Nps-Cur revealed a biphasic pattern with an initial exponential phase followed by a slow release phase. Cellular internalization of Nps-Cur was confirmed by fluorescence and confocal microscopy with a wide distribution of the fluorescence in the cytoplasm and within the nucleus. The prepared nanoformulation was characterized for cellular toxicity and biological activity. Cytotoxicity assays showed that void PLGA-nanoparticles (Nps) and curcumin-loaded PLGA nanoparticles (Nps-Cur) were nontoxic to human neuroblastoma SK-N-SH cells. Moreover, Nps-Cur was able to protect SK-N-SH cells against H2O2 and prevent the elevation of reactive oxygen species and the consumption of glutathione induced by H2O2. Interestingly, Nps-Cur was also able to prevent the induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2. Taken together, these results suggest that Nps-Cur could be a promising drug delivery strategy to protect neurons against oxidative damage as observed in Alzheimer's disease. /Curcumin-loaded PLGA nanoparticles/[Doggui S et al; J Alzheimers Dis 30 (2): 377-92 (2012)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: Recent studies report curcumin nanoformulation(s) based on polylactic-co-glycolic acid (PLGA), beta-cyclodextrin, cellulose, nanogel, and dendrimers to have anticancer potential. However, no comparative data are currently available for the interaction of curcumin nanoformulations with blood proteins and erythrocytes. The objective of this study was to examine the interaction of curcumin nanoformulations with cancer cells, serum proteins, and human red blood cells, and to assess their potential application for in vivo preclinical and clinical studies. The cellular uptake of curcumin nanoformulations was assessed by measuring curcumin levels in cancer cells using ultraviolet-visible spectrophotometry. Protein interaction studies were conducted using particle size analysis, zeta potential, and Western blot techniques. Curcumin nanoformulations were incubated with human red blood cells to evaluate their acute toxicity and hemocompatibility. Cellular uptake of curcumin nanoformulations by cancer cells demonstrated preferential uptake versus free curcumin. Particle sizes and zeta potentials of curucumin nanoformulations were varied after human serum albumin adsorption. A remarkable capacity of the dendrimer curcumin nanoformulation to bind to plasma protein was observed, while the other formulations showed minimal binding capacity. Dendrimer curcumin nanoformulations also showed higher toxicity to red blood cells compared with the other curcumin nanoformulations. PLGA and nanogel curcumin nanoformulations appear to be very compatible with erythrocytes and have low serum protein binding characteristics, which suggests that they may be suitable for application in the treatment of malignancy. These findings advance our understanding of the characteristics of curcumin nanoformulations, a necessary component in harnessing and implementing improved in vivo effects of curcumin./Molecular carrier system/[Yallapu MM et al; Int J Nanomedicine 6: 2779-90 (2011)] **PEER REVIEWED** PubMed Abstract Full text: PMC3225220
  • ALTERNATIVE and IN VITRO TESTS: The anti-inflammatory and antiproliferative agent curcumin has poor oral bioavailability and solubility in plasma. Liposomal formulations have therefore been developed, but the toxicity of these preparations is not yet established. /Researchers/ investigated the influence of free and liposomally formulated curcumin on human red blood cell (RBC) morphology in vitro. EDTA-buffered whole blood from two healthy individuals was incubated with different concentrations (1, 10, 100 ug/mL) of free or liposomal curcumin. RBC morphology and mean cellular volume (MCV) were examined at up to 4 hours of incubation. Dose-dependent echinocyte formation was observed after incubation with free, and liposomal curcumin, with a threshold concentration of 10 ug/mL and peak effect after 30 minutes. A concomitant increase in mean cellular volume was detectable. Curcumin and liposomal curcumin cause dose-dependent changes in the shape of RBCs. This effect may represent an early sign of dose-limiting toxicity following intravenous administration./Liposomal curcumin/[Storka A et al; Anticancer Res 33 (9): 3629-34 (2013)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: This study investigated the inhibitory effects of curcumin on proliferation of hematological malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacetylation levels. The effects of curcumin and histone deacetylase inhibitor trichostatin A (TSA) on the growth of Raji cells were tested by MTT assay. The expression of acetylated histone-3 (H(3)) in Raji, HL60 and K562 cells, and peripheral blood mononuclear cells (PBMCs) treated with curcumin or TSA was detected by immunohistochemistry and FACS. The results showed curcumin inhibited proliferation of Raji cells significantly in a time- and dose-dependent fashion, while exhibited low toxicity in PBMCs. Curcumin induced up-regulation of the expression of acetylated H(3) dose-dependently in all malignant cell lines tested. In conclusion, curcumin inhibited proliferation of Raji cells selectively, enhanced the level of acetylated (H(3)) in Raji, HL60, and K562 cells, which acted as a histone deacetylase inhibitor like TSA. Furthermore, up-regulation of H(3) acetylation may play an important role in regulating the proliferation of Raji cells.[Hu J et al; J Huazhong Univ Sci Technolog Med Sci 29 (1): 25-8 (2009)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: Turmeric, the powdered dry rhizome of the Curcuma longa plant, and curcumin, the major anti-oxidant constituent of turmeric, have been shown to possess chemopreventive activity. To elucidate the possible interaction of turmeric and curcumin with conjugation reactions, which in many cases are involved in the activation of procarcinogens, /researchers/ measured their effects in the conjugation of 1-naphthol in Caco-2 cells, a human colon carcinoma cell line, within a 24 hr period. Turmeric exhibits inhibitory activity toward both sulfo- and glucuronosyl conjugations of 1-naphthol at approximately the same levels (IC(50)=0.24 and 0.29 mg/mL, respectively). Curcumin inhibits sulfo-conjugation at lower concentrations (IC(50)=9.7 ug/mL), but only showed weak inhibition toward glucuronosyl conjugation of 1-naphthol in Caco-2 cells. In addition, turmeric was found to strongly inhibit in vitro phenol sulfotransferase (SULT) activity and demonstrate moderate inhibitory properties against UDP-glucuronosyl transferase (UGT) activity in Caco-2 cells (IC(50)=0.17 mg/mL and 0.62 mg/mL, respectively). Curcumin also strongly inhibits in vitro phenol sulfotransferase activity with an IC(50) of 2.4 ug/mL. Moreover, and in contrast to the moderate inhibition of UGT activity by turmeric and curcumin, both induce the expression of the UGT1A1 and UGT1A6 genes, revealed by real-time PCR analysis. These findings are indicative of a possible interaction of both turmeric and curcumin with conjugation reactions in the human intestinal tract and colon. This in turn may affect the bioavailability of therapeutic drugs and toxicity levels of environmental chemicals, particularly procarcinogens.[Naganuma M et al; Biol Pharm Bull 29 (7): 1476-9 (2006)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: Using absorption and fluorescence spectroscopic methods, quantitative cellular uptake of curcumin, an antioxidant and anti-tumor agent from Curcuma longa, was calculated in two types of normal cells: spleen lymphocytes, and NIH3T3 and two tumor cell lines: EL4 and MCF7. Both the uptake and fluorescence intensity of curcumin were significantly higher in tumor cells compared to the normal cells. A linear dependency on the uptake was observed with treatment concentration of curcumin. Using laser confocal microscopy, intracellular localization of curcumin was monitored and the results indicated that curcumin is located both in the cell membrane and the nucleus. Sub-cellular fractionation of curcumin-loaded MCF7 cells supported the differential distribution of curcumin in membrane, cytoplasm and nuclear compartments of cell with maximum localization in the membrane. Cytotoxicity studies in different cell lines indicated that the toxicity of curcumin increased with increasing uptake.[Kunwar A et al; Biochim Biophys Acta 1780 (4): 673-9 (2008)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, has been considered as nutraceutical because of its strong anti-inflammatory, antitumour and antioxidant properties. The aim of /the/ present study was to investigate whether curcumin can protect lung epithelial cells from the cytotoxic, genotoxic and inflammatory effects associated with quartz (DQ12) exposure. Electron paramagnetic resonance (EPR) measurements using the spin-trap DMPO demonstrated that curcumin reduces hydrogen peroxide-dependent hydroxyl-radical formation by quartz. Curcumin was also found to reduce quartz-induced cytotoxicity and cyclooxygenase 2 (COX-2) mRNA expression in RLE-6TN rat lung epithelial cells (RLE). Curcumin also inhibited the release of macrophage inflammatory protein-2 (MIP-2) from RLE cells as observed upon treatment with interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). However, curcumin failed to protect the RLE cells from oxidative DNA damage induced by quartz, as shown by formamidopyrimidine glycosylase (FPG)-modified comet assay and by immunocytochemistry for 8-hydroxydeoxyguanosine. In contrast, curcumin was found to be a strong inducer of oxidative DNA damage itself at non-cytotoxic and anti-inflammatory concentrations. In line with this, curcumin also enhanced the mRNA expression of the oxidative stress response gene heme oxygenase-1 (ho-1). Curcumin also caused oxidative DNA damage in NR8383 rat alveolar macrophages and A549 human lung epithelial cells. Taken together, these observations indicate that one should be cautious in considering the potential use of curcumin in the prevention or treatment of lung diseases associated with quartz exposure.[Li H et al; Toxicol Appl Pharmacol 227 (1): 115-24 (2008)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Curcumin ... caused oxidative DNA damage in ... A549 human lung epithelial cells.[Li H et al; Toxicol Appl Pharmacol 227 (1): 115-24 (2008)] **PEER REVIEWED** PubMed Abstract
  • HUMAN EXPOSURE STUDIES: ...Patients with advanced colorectal cancer receiving Curcuma extract daily for up to 4 months were examined physically and blood samples were taken on days 1, 2, 8 and 29 of treatment and monthly thereafter. Blood samples were analysed for full blood cell count, concentrations of urea, electrolytes and markers of liver and bone function. Curcuma extract was administered at a dose equivalent to 26, 72, 108, 144 or 180 mg of diferuloylmethane, with three patients receiving each dose. The only adverse effects reported were gastrointestinal symptoms. During the first month of treatment, one patient receiving diferuloylmethane at a dose of 108 mg per day experienced nausea, which resolved spontaneously without discontinuing the treatment. Two patients, who received diferuloylmethane at a dose of 72 or 180 mg per day, respectively, experienced diarrhea. In the absence of controls, and in view of the clinical conditions of the patients, it is not clear whether these symptoms were related to treatment.[WHO ; WHO Food Additives Series 52 Curcumin (addendum); Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v52je04.htm] **PEER REVIEWED**
  • HUMAN EXPOSURE STUDIES: Twenty-five patients with conditions indicating a high risk of malignancy were given diferuloylmethane (purity, 99.3%) for 3 months. The starting dose was 500 mg/day, which was increased stepwise to 1000, 2000, 4000, 8000 and finally 12 000 mg/day. The patients received regular followup, including physical examination, weekly hemogram, and measurement of blood electrolytes and biochemistry parameters every 2 weeks. No adverse effects were reported at doses of up to 8000 mg/day.[WHO ; WHO Food Additives Series 52 Curcumin (addendum); Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v52je04.htm] **PEER REVIEWED**
  • IMMUNOTOXICITY: Curcumin is a multi-functional and pharmacologically safe natural agent. Used as a food additive for centuries, it also has anti-inflammatory, anti-virus and anti-tumor properties. /The authors/ previously found that it is a potent inhibitor of cyclosporin A (CsA)-resistant T-cell co-stimulation pathway. It inhibits mitogen-stimulated lymphocyte proliferation, NFkappaB activation and IL-2 signaling. In spite of its safety and efficacy, the in vivo bioavailability of curcumin is poor, and this may be a major obstacle to its utility as a therapeutic agent. Liposomes are known to be excellent carriers for drug delivery. In this in vitro study, /investigators/ report the effects of different liposome formulations on curcumin stability in phosphate buffered saline (PBS), human blood, plasma and culture medium RPMI-1640+10% FBS (pH 7.4, 37 degrees C). Liposomal curcumin had higher stability than free curcumin in PBS. Liposomal and free curcumin had similar stability in human blood, plasma and RPMI-1640+10% FBS. /They/ looked at the toxicity of non-drug-containing liposomes on (3)H-thymidine incorporation by concanavalin A (Con A)-stimulated human lymphocytes, splenocytes and Epstein-Barr virus (EBV)-transformed human B-cell lymphoblastoid cell line (LCL). /They/ found that dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) were toxic to the tested cells. However, addition of cholesterol to the lipids at DMPC:DMPG:cholesterol=7:1:8 (molar ratio) almost completely eliminated the lipid toxicity to these cells. Liposomal curcumin had similar or even stronger inhibitory effects on Con A-stimulated human lymphocyte, splenocyte and LCL proliferation. /The authors/conclude that liposomal curcumin may be useful for intravenous administration to improve the bioavailability and efficacy, facilitating in vivo studies that could ultimately lead to clinical application of curcumin./Liposomal curcumin/[Chen C et al; Int J Pharm 366 (1-2): 133-9 (2009)] **PEER REVIEWED** PubMed Abstract
  • OTHER TOXICITY INFORMATION: ... Establishing the entire toxicological profile is thus indispensable for proving the human safety of nanocarriers, which was the primary objective of the current investigation. The developed curcumin loaded polymeric nanoparticles of Eudragit S100 were subjected to various toxicological evaluations which included acute-toxicity study, sub-acute-toxicity study (28 days) and various genotoxicity studies like in vivo Micronucleus assay, in vivo Chromosomal Aberration assay and in vivo Comet assay. The formulation was found to be non-toxic at the dose equivalent to 2000 mg/kg of body weight of curcumin in the acute-toxicity study. Sub-acute-toxicity study proved the safety of the formulation for prolonged administration at the commonly used therapeutic dose of 100 mg/kg of body weight of curcumin and at twice the therapeutic dose. Genotoxicity studies proved the cellular safety of the developed formulation at the therapeutic dose, and even at doses equivalent to thrice the therapeutic dose. Thus the developed curcumin loaded polymeric nanoparticles of Eudragit S100 were found to be safe for oral administration for a short as well as a prolonged duration./ pH-sensitive nanoparticles of curcumin/[Dandekar P et al; Food Chem Toxicol 48 (8-9): 2073-89 (2010)] **PEER REVIEWED** PubMed Abstract
  • OTHER TOXICITY INFORMATION: Biomedical investigations of curcumin (and curcuminoids) have provided evidence of a wide range of molecular and cellular activities, most related to redox reactions and signal transduction. The main goal of the present study was to compare antioxidant activities of curcumin with those of resveratrol, a polyphenol present in some dietary plants such as Vitis vinifera (L.) and Arachis hypogaea (L.) and many other, non-dietary plants. Combinations of the two were also examined for potential synergism in a heme-enhanced oxidation reaction. Curcumin exhibited antioxidant effects at all time points (1-5 min; 10 uM), e.g., 30.5 +/- 11.9% (SEM) oxidation relative to controls without phytochemicals (p < 0.01) at 3 min, a time chosen for comparisons. The same concentration of resveratrol exhibited about half of curcumin's activity. Curcumin and resveratrol together (5 uM each) resulted in a synergistic antioxidant effect: 15.5 +/- 1.7% greater than an average of individual activities. This synergy was significantly greater (p < 0.05; about 4-fold) than that of curcumin together with the flavonol quercetin. In conclusion, curcumin is a potent antioxidant in a reaction that may be relevant to in vivo toxicity. In relation to two other well-known antioxidants, curcumin shows significantly greater synergism with resveratrol than with quercetin.[Aftab N, Vieira A; Phytother Res 24 (4): 500-2 (2010)] **PEER REVIEWED** PubMed Abstract
  • OTHER TOXICITY INFORMATION:... As a diet-derived agent, curcumin has no severe toxicity except for minor gastrointestinal side effects even up to the dosage of 8 grams for 3 months...[Fan X et al; Curr Pharm Des 19 (11): 2011-31 (2013)] **PEER REVIEWED** PubMed Abstract

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Non-Human Toxicity Excerpts

  • ALTERNATIVE and IN VITRO TESTS: Curcumin, a component of turmeric spice that imparts flavor and color to curry, is thought to possess anti-inflammatory and antioxidant properties in biological tissues. However, while such efficacies have been described in the context of carcinogenesis, the impact of curcumin on normal cell cycle regulation is poorly understood. Here, /investigators/ provide evidence of curcumin toxicity in proliferating bovine aortic endothelial cells, at concentrations relevant to the diet and below those previously reported in cancer models. Upon confirming curcumin's ability to upregulate hemeoxygenase-1 in a dose-dependent fashion, we found the minimally efficacious curcumin concentration to also inhibit endothelial cell DNA synthesis. Moreover, curcumin concentrations below the minimum 2 uM threshold required to induce hemeoxygenase-1 bound tubulin protein in vitro and triggered hallmark evidence of mitotic catastrophe in vivo. Concentrations as low as 0.1uM curcumin led to disproportionate DNA segregation, karyorrhexis, and micronucleation in proliferating endothelial cells. While suggesting a mechanism by which physiological curcumin concentrations inhibit cell cycle progression, these findings describe heretofore unappreciated curcumin toxicity with potential implications for endothelial growth, development, and tissue healing.[Jackson SJ et al; Food Chem Toxicol 60 :431-8 (2013)] **PEER REVIEWED** PubMed Abstract Full text: PMC3954605
  • ALTERNATIVE and IN VITRO TESTS: Curcumin, diferuloyl methane, the yellow pigment component of the curry spice turmeric (Curcuma longa), has immense biological effects and has recently drawn considerable attention. Curcumin has antibacterial, antiviral, antiinflammatory, and anticancer properties. It has shown a lack of toxicity in animals and human clinical trials. Yet, its effect on reproduction has not been examined. The present study was conducted to examine if curcumin affects sperm function in vitro and fertility in vivo. Sperm (human and murine) were collected and incubated with curcumin to examine the effect on motility, capacitation/acrosome reaction, and in vitro fertilization. The effect on in vivo fertility using the mouse model was also examined. Incubation of sperm with curcumin caused a concentration-dependent decrease in sperm forward motility, capacitation/acrosome reaction, and murine fertilization in vitro. At higher concentrations, there was a complete block of sperm motility and function within 5-15 min. Administration of curcumin, especially intravaginally, caused a significant (P<0.001) reduction in fertility. The antifertility effect of curcumin was reversible. This ... study /repors/ the inhibitory effect of curcumin on sperm function, fertilization, and fertility. The findings suggest that curcumin may constitute a double-edged sword to block conception, infection, and cancer, thus providing an ideal contraceptive.[Naz RK; Mol Reprod Dev 78 (2): 116-23 (2011)] **PEER REVIEWED** PubMed Abstract
  • ALTERNATIVE and IN VITRO TESTS: In the previous study, we unraveled the unique "erasure strategy" during the mouse spermiogenesis. Chromatin associated proteins sequentially disassociated from the spermatid chromosome, which led to the termination of transcription in elongating spermatids. By this process, a relatively naive paternal chromatin was generated, which might be essential for the zygotic development. /The authors/ supposed the regulation of histone acetylation played an important role throughout this "erasure" process. In order to verify this hypothesis, /they/ treated mouse spermatids in vitro by histone acetylase (HAT) inhibitor Curcumin. /These/ results showed an inhibiting effect of Curcumin on the growth of germ cell line in a dose-dependent manner. Accordingly, the apoptosis of primary haploid spermtids was increased by Curcumin treatment. As expected, the acetylated histone level was downregulated. Furthermore, /the authors/ found the transcription in spermatids ceased in advance, the dynamics of chromatin associated factors was disturbed by Curcumin treatment. The regulation of histone acetylation should be one of the core reprogramming mechanisms during the spermiogenesis. The reproductive toxicity of Curcumin needs to be thoroughly investigated, which is crucial for its further clinical application.[Xiaoyu Xia et al; PLoS One; 7(11): e48673 (2012)] **PEER REVIEWED** PubMed Abstract Full text: PMC3492465
  • ALTERNATIVE and IN VITRO TESTS: Using absorption and fluorescence spectroscopic methods, quantitative cellular uptake of curcumin, an antioxidant and anti-tumor agent from Curcuma longa, was calculated in two types of normal cells: spleen lymphocytes, and NIH3T3 and two tumor cell lines: EL4 and MCF7. Both the uptake and fluorescence intensity of curcumin were significantly higher in tumor cells compared to the normal cells. A linear dependency on the uptake was observed with treatment concentration of curcumin. Using laser confocal microscopy, intracellular localization of curcumin was monitored and the results indicated that curcumin is located both in the cell membrane and the nucleus. Sub-cellular fractionation of curcumin-loaded MCF7 cells supported the differential distribution of curcumin in membrane, cytoplasm and nuclear compartments of cell with maximum localization in the membrane. Cytotoxicity studies in different cell lines indicated that the toxicity of curcumin increased with increasing uptake.[Kunwar A et al; Biochim Biophys Acta 1780 (4): 673-9 (2008)] **PEER REVIEWED** PubMed Abstract
  • BEHAVIORAL STUDIES: Chronic stress occurs in everyday life and induces impaired spatial cognition, neuroendocrine and plasticity abnormalities. A potential therapeutic for these stress related disturbances is curcumin, derived from the curry spice turmeric. Previously /researchers/ demonstrated that curcumin reversed the chronic stress-induced behavioral deficits in escape from an aversive stimulus, however the mechanism behind its beneficial effects on stress-induced learning defects and associated pathologies are unknown. This study /in male Sprague Dawley rats/ investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction in a water maze task and on measures related neuroendocrine and plasticity changes. The results showed that memory deficits were reversed with curcumin in a dose dependent manner, as were stress-induced increases in serum corticosterone levels. These effects were similar to positive antidepressant imipramine. Additionally, curcumin prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus, as assessed by the changes in branch points and dendritic length. In primary hippocampal neurons it was shown that curcumin or imipramine protected hippocampal neurons against corticosterone-induced toxicity. Furthermore, the portion of calcium/calmodulin kinase II (CaMKII) that is activated (phosphorylated CaMKII, pCaMKII), and the glutamate receptor sub-type (NMDA(2B)) expressions were increased in the presence of corticosterone. These effects were also blocked by curcumin or imipramine treatment. Thus, curcumin may be an effective therapeutic for learning and memory disturbances as was seen within these stress models, and its neuroprotective effect was mediated in part by normalizing the corticosterone response, resulting in down-regulating of the pCaMKII and glutamate receptor levels.[Xu Y et al; Neuropharmacology 57 (4): 463-71 (2009)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, has been considered as nutraceutical because of its strong anti-inflammatory, antitumour and antioxidant properties. The aim of our present study was to investigate whether curcumin can protect lung epithelial cells from the cytotoxic, genotoxic and inflammatory effects associated with quartz (DQ12) exposure. Electron paramagnetic resonance (EPR) measurements using the spin-trap DMPO demonstrated that curcumin reduces hydrogen peroxide-dependent hydroxyl-radical formation by quartz. Curcumin was also found to reduce quartz-induced cytotoxicity and cyclooxygenase 2 (COX-2) mRNA expression in RLE-6TN rat lung epithelial cells (RLE). Curcumin also inhibited the release of macrophage inflammatory protein-2 (MIP-2) from RLE cells as observed upon treatment with interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). However, curcumin failed to protect the RLE cells from oxidative DNA damage induced by quartz, as shown by formamidopyrimidine glycosylase (FPG)-modified comet assay and by immunocytochemistry for 8-hydroxydeoxyguanosine. In contrast, curcumin was found to be a strong inducer of oxidative DNA damage itself at non-cytotoxic and anti-inflammatory concentrations. In line with this, curcumin also enhanced the mRNA expression of the oxidative stress response gene heme oxygenase-1 (ho-1). Curcumin also caused oxidative DNA damage in NR8383 rat alveolar macrophages and A549 human lung epithelial cells. Taken together, these observations indicate that one should be cautious in considering the potential use of curcumin in the prevention or treatment of lung diseases associated with quartz exposure.[Li H et al; Toxicol Appl Pharmacol 227 (1): 115-24 (2008)] **PEER REVIEWED** PubMed Abstract
  • GENOTOXICITY: Curcumin was found to be negative when tested for mutagenicity using the Salmonella/microsome preincubation assay, using the standard protocol approved by the National Toxicology Program (NTP). Curcumin was tested in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat and hamster liver S-9, at doses of 0.001, 0.003, 0.010, 0.033, 0.100, 0.333, 1.000, and 3.333 mg/plate. The highest ineffective dose tested in any S. typhimurium strain was 3.333 mg/plate. Precipitate was observed in many of the cultures at this dose as well as some clearing of the background bacterial lawn.[Mortelmans K et al; Environ Mutagen 8:1-119 (1986)] **PEER REVIEWED**
  • GENOTOXICITY: In vivo, a curcumin preparation of unknown purity administered to mice by intraperitoneal injection did not induce micronuclei in bone marrow cells, whereas a low level of chromosomal aberrations was reported in the same cell population. In another in vivo study in mice injected with curcumin of unknown purity there was some evidence of SCE induction at low frequency above 25 mg/kg bw, while in rats fed curcumin of unknown purity there was equivocal evidence for the induction of chromosomal aberrations.[WHO ; WHO Food Additives Series 35 Curcumin; Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v35je09.htm] **PEER REVIEWED**
  • GENOTOXICITY: Micronucleus in vivo assay perfomed in male Fischer 344 rats was negative.[NTP; Testing Status of Agents at NTP for Curcumin (CAS RN 458-37-7); Available from, as of November 6, 2013: http://ntp.niehs.nih.gov/?objectid=BD112293-123F-7908-7B53F5979AE705B1] **PEER REVIEWED**
  • GENOTOXICITY: There was a significant time-dependent reduction in the number of radiation-induced micronucleated polychromatic erythrocytes in mice given single gavage doses of 5, 10 or 20 mg/kg bw curcumin in peanut oil.[WHO ; WHO Food Additives Series 35 Curcumin; Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v35je09.htm] **PEER REVIEWED**
  • GENOTOXICITY: Using the Ames test, curcumin itself a non-mutagen, inhibited the mutagenic effects of chili extract and capsaicin. Similarly, curcumin was reported to inhibit the activity of known environmental mutagens which require metabolic activation, although it was reported to be ineffective against mutagens which do not require metabolic activation.[WHO ; WHO Food Additives Series 35 Curcumin; Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v35je09.htm] **PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: An acute toxicity study showed that mice treated with ...Zn(II)-curcumin (2 g/kg) manifested no abnormal signs./Zinc(II)-curcumin complex/[Mei X et al; Chem Biol Interact 181 (3): 316-21 (2009)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: A two-generation study in Wistar rats was conducted according to OECD guideline 416 (May 1983) using curcumin comprising 80% diferuloylmethane, 99% total curcuminoids. ...Groups of 30 male and 30 female rats were fed diets containing curcumin at a concentration of 0, 1500, 3000 or 10 000 mg/kg of diet starting from 10 weeks before the mating period and throughout mating. Treatment of females continued throughout pregnancy and weaning of the offspring. The total periods of treatment were 21 weeks for the parental generation and 24 weeks for the F1 generation. On postnatal day 4, the litter sizes of the F1 offspring were standardized to a maximum of eight. After weaning, 30 male and 30 females of the F1 generation were selected to become the parents of the F2 generation. Parents were observed for clinical signs, body weights, food intake, cohabitation interval and duration of gestation. Pups were weighed on postnatal days 1, 4, 7, 14 and 21. All parents, F1 weanlings not selected for mating and all F2 weanlings were subjected to complete necropsy at terminal sacrifice. The concentrations used corresponded to doses of 0, 130-140, 250-290 or 850-960 mg/kg bw per day in males, and 0, 160, 310-320 or 1000-1100 mg/kg bw per day in females. The following indices were calculated: male and female fertility index, percentage of matings resulting in pregnancy, number of implantations, percentage of pregnancies resulting in birth of live litters, percentage of live pups born, postimplantation loss, mean litter size and mean viable litter size, live birth index, percentage survival of pups at postnatal days 4, 7, 14 and 21. Ovaries, uterus, vagina/cervix, testes, epididymides, seminal vesicles, prostate, coagulating glands, liver, kidney, pituitary and adrenals were examined histologically. There was a dose-related decrease in body-weight gain in the dams of the parental generation during days 10-15 of gestation, which was statistically significantly different from that of controls (body-weight gains, >80% that of controls) at the intermediate and highest doses. At this time, body weights were reported to be below the range of values for the historical controls. However, maternal body weights did not differ significantly between groups at the end of gestation. The mean body weights of the F2 offspring (both sexes combined) were significantly decreased on postnatal days 1 and 7 at the intermediate dose, and on postnatal days 7, 14 and 21 at the highest dose. A dose-related trend was apparent, but the effect was small, with average body weights being >90% that of the control pups, and the observed changes were reported to be within the range of the data for historical controls. There were no other effects on general health, body weight, pup survival and fertility indices in either generation. The effects at the intermediate dose were observed at isolated time-points only and were considered to be incidental; and therefore this dose, equal to 250-320 mg/kg bw per day for the F1 generation, was the NOEL[WHO ; WHO Food Additives Series 52 Curcumin (addendum); Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v52je04.htm] **PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Curcumin, a polyphenol derived from the rhizome turmeric, has potential as an anticancer agent. We synthesized an amphipathic/surfactant pegylated curcumin (curcumin-PEG) designed for parenteral administration. Objectives of these investigations were to assess side-effects of a therapeutic regimen of curcumin-PEG in a preclinical model. Intraperitoneal (ip) tumor burdens were reduced in athymic female mice grafted with human SKOV-3 ovarian adenocarcinoma cells and injected intravenously (iv) with curcumin-PEG. There were no gross anatomical or histopathological effects detected in non-reproductive organs. Uteri (luminal fluid imbibition) and ovaries (decreased folliculogenesis) were affected by treatment. Curcumin-PEG ip hastened the onset of puberty in immature female mice. Live births were reduced in mature females housed with males and treated iv with curcumin-PEG; mating (vaginal plugs) was not affected. Accessory gland weights, testicular testosterone concentrations, and spermatogenesis were diminished in mature male mice following iv curcumin-PEG. Estrogenic/antiandrogenic and pregnancy-disrupting effects of a water soluble/bioavailable curcumin were demonstrated. /Curcumin-PEG)/[Murphy CJ et al; Reprod Toxicol 34 (1): 120-4 (2012)] **PEER REVIEWED** PubMed Abstract Full text: PMC3387530
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Embryotoxic and teratogenic effects of curcumin on the development of zebrafish embryo were investigated in this study. The LD(50) values of curcumin (24-hr incubation) were estimated at 7.5 uM and 5 uM for embryos and larvae, respectively. The developmental defects caused by curcumin treatments include bent or hook-like tails, spinal column curving, edema in pericardial sac, retarded yolk sac resorption, and shorter body length. In curcumin-treated larvae, fluorescence signals of curcumin were found in edamae sac and some skin cells. Together, these results indicate that zebrafish are suitable model organisms to study the toxic effects of curcumin.[Wu JY et al; Biol Pharm Bull 30 (7): 1336-9 (2007)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: The reproductive toxicity of curcumin, turmeric yellow, in Wistar rats was studied in order to generate additional relevant toxicity information for the use of curcumin in humans by oral administration. The two generation reproduction study was designed and conducted in accordance with OECD Guideline No. 416... The curcumin, mixed in the experimental diet at the concentrations of 1500, 3000 and 10,000 ppm was fed to three groups of rats, i.e., low, mid and high dose groups, and studied for two successive generations. A concurrent control group received experimental diet without the curcumin mixture. There were no treatment related adverse toxicological effects in the parental animals. No gross or microscopic changes were observed in any of the organs. None of the reproductive parameters were affected and there were no effects on the offspring other than a small reduction in pre-weaning body weight gain of the F2 pups at the highest dose level. It was concluded that the no observed adverse effect level (NOAEL) for reproductive toxicity of curcumin, fed in the diet for two successive generations to rats in this study was 10,000 ppm, which is equivalent to 847 and 959 mg/kg bodyweight (bw) per day for male rats and 1043 and 1076 for females for F0 and F1 generations, respectively...The JECFA group considered that the small body weight reduction in the F2 pups of the highest dose group prevented this from being regarded as a no adverse effect level, and so allocated an ADI for curcumin of 0-3 mg/kg bw based on the intake of 250-320 mg/kg bw in the mid-dose group as the NOEL.[Ganiger S et al; Food Chem Toxicol 45 (1): 64-9 (2007)] **PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: 100 mg/kg of curcumin admin orally for 6 consecutive days produced gastric ulceration in albino rats due to reduction in the mucin content of gastric juice.[GUPTA ET AL; INDIAN J MED RES 71(MAY) 806 (1980)] **PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Curcumin, a polyphenol, is obtained from turmeric, the ground rhizomes of Curcuma longa L. Extensive research over the past half century has revealed several health benefits of curcumin. The objective of the present study was to investigate potential adverse effects, if any, of a novel solid lipid curcumin particle (SLCP) preparation in rats following acute and subchronic administration. The oral LD50 of the preparation in rats as well as in mice was found to be greater than 2000 mg/kg body weight (bw). In the subchronic toxicity study, Wistar rats (10/sex/group) were administered via oral gavage 0 (control), 180, 360, and 720 mg/kg bw/day of SLCP preparation for 90 days. Administration of the curcumin preparation did not result in any toxicologically significant treatment-related changes in clinical (including behavioral) observations, ophthalmic examinations, body weights, body weight gains, feed consumption, and organ weights. No adverse effects of the curcumin preparation were noted on the hematology, serum chemistry parameters, and urinalysis. Terminal necropsy did not reveal any treatment-related gross or histopathology findings. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for this standardized novel curcumin preparation was determined as 720 mg/kg bw/day, the highest dose tested. /Solid lipid curcumin particle/[Dadhaniya P et al; Food Chem Toxicol 49 (8): 1834-42 (2011)] **PEER REVIEWED** PubMed Abstract
  • OTHER TOXICITY INFORMATION: Curcumin, the principal curcuminoid of the popular Indian spice turmeric, has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin is a major challenge in its development as a useful drug. To enhance the aqueous solubility and bioavailability of curcumin, attempts have been made to encapsulate it in liposomes, polymeric nanoparticles (NPs), lipid-based NPs, biodegradable microspheres, cyclodextrin, and hydrogels. In this work, we attempted to entrap curcumin in novel self-assembled dipeptide NPs containing a nonprotein amino acid, alpha, beta-dehydrophenylalanine, and investigated the biological activity of dipeptide-curcumin NPs in cancer models both in vitro and in vivo. Of the several dehydrodipeptides tested, methionine-dehydrophenylalanine was the most suitable one for loading and release of curcumin. Loading of curcumin in the dipeptide NPs increased its solubility, improved cellular availability, enhanced its toxicity towards different cancerous cell lines, and enhanced curcumin's efficacy towards inhibiting tumor growth in Balb/c mice bearing a B6F10 melanoma tumor. These novel, highly biocompatible, and easy to construct dipeptide NPs with a capacity to load and release curcumin in a sustained manner significantly improved curcumin's cellular uptake without altering its anticancer or other therapeutic properties. Curcumin-dipeptide NPs also showed improved in vitro and in vivo chemotherapeutic efficacy compared to curcumin alone. Such dipeptide-NPs may also improve the delivery of other potent hydrophobic drug molecules that show poor cellular uptake, bioavailability, and efficacy./ Dipeptide-curcumin NPs/[Alam S et al; Int J Nanomedicine 7: 4207-22 (2012)] **PEER REVIEWED** PubMed Abstract Full text: PMC3418106
  • OTHER TOXICITY INFORMATION: In this study, the R7L10 peptide, which is composed of a 7-arginine stretch and a 10-leucine stretch, was evaluated as a carrier for the combined delivery of curcumin and plasmid DNA (pDNA) into the lungs. Curcumin is a natural product with anti-inflammatory and anti-tumor effects. Curcumin-loaded R7L10 (R7L10-curucmin) was prepared by an oil-in-water (O/W) emulsion/solvent evaporation method. In vitro transfection showed that R7L10-curcumin had higher transfection efficiency than R7L10. Although R7L10-curcumin had lower transfection efficiency than polyethylenimine (25 kDa, PEI25k) and lipofectamine, R7L10-curcumin had lower cytotoxicity. In gel retardation assays and heparin competition assays, R7L10-curcumin formed a more stable complex with pDNA than R7L10. The intracellular curcumin delivery efficiency of R7L10-curcumin was higher than that of curcumin only. Furthermore, R7L10-curcumin more efficiently decreased TNF-alpha level in lipopolysaccharide (LPS)-activated Raw264.7 macrophage cells than curcumin only. For in vivo evaluation, pDNA/R7L10-curcumin complexes were administered into mouse lungs by intratracheal instillation. The results revealed that R7L10-curcumin delivered pDNA more efficiently than R7L10, poly-L-lysine (PLL), or PEI25k. In addition, R7L10-curcumin decreased TNF-alpha level in lung tissues in an acute lung injury mouse model. In contrast to PEI25k, R7L10-curcumin did not show liver toxicity after intravenous injection. These results suggest that R7L10-curcumin is a useful carrier for the combined delivery of curcumin and pDNA into the lungs./ Molecular carrier system/[Park JH et al; Biomaterials 33 (27): 6542-50 (2012)] **PEER REVIEWED** PubMed Abstract
  • OTHER TOXICITY INFORMATION: Larval feeding with curcumin induces an extended health span with significantly increased median and maximum longevities in the adult fly. This phenotype is diet insensitive and shows no additive effect on longevity when combined with an adult dietary restriction (DR) diet, suggesting that curcumin and DR operate via the same or overlapping pathways for this trait. This treatment significantly slows the aging rate so that it is comparable with that of genetically selected long lived animals. The larval treatment also enhances the adult animal's geotactic activity in an additive manner with DR, suggesting that curcumin and DR may use different pathways for different traits. Feeding the drug to adults during only the health span also results in a significantly extended health span with increased median and maximum life span. This extended longevity phenotype is induced only during these stage-specific periods. Feeding adults with the drug over their whole life results in a weakly negative effect on median longevity with no increase in maximum life span. There are no negative effects on reproduction, although larval curcumin feeding increases development time, and also apparently accelerates the normal late-life neuromuscular degeneration seen in the legs. Gene expression data from curcumin-fed larvae shows that the target of rapamycin (TOR) pathway is inhibited in the larvae and the young to midlife adults, although several other genes involved in longevity extension are also affected. These data support the hypothesis that curcumin acts as if it is a DR mimetic nutraceutical. These data also suggest that the search for DR mimetics may be enhanced by the use of stage-specific screening of candidate molecules.[Soh JW et al; Exp Geronto 48 (2): 229-39 (2013)] **PEER REVIEWED** PubMed Abstract

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Mice oral more than 2000 mg/kg bw /Solid lipid curcumin particle/[Dadhaniya P et al; Food Chem Toxicol 49 (8): 1834-42 (2011)] **PEER REVIEWED** PubMed Abstract
  • LD50 Mice oral more than 2000 mg/kg[NTP; Toxicology & Carcinogenesis Studies of Turmeric Oleoresin (Major Component 79%-85% Curcumin in F344/N Rats and B6C3F1 Mice (Feed Studies). Technical Report Series No. 427 (1993) NIH Publication No. 93-3158; Available from, as of November 6, 2013: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr427.pdf] **PEER REVIEWED**
  • LD50 Rats oral more than 2000 mg/kg bw /Solid lipid curcumin particle/[Dadhaniya P et al; Food Chem Toxicol 49 (8): 1834-42 (2011)] **PEER REVIEWED** PubMed Abstract
  • LD50 Rats oral more than 5000 mg/kg /Curcumin oil/[NTP; Toxicology & Carcinogenesis Studies of Turmeric Oleoresin (Major Component 79%-85% Curcumin in F344/N Rats and B6C3F1 Mice (Feed Studies). Technical Report Series No. 427 (1993) NIH Publication No. 93-3158; Available from, as of November 6, 2013: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr427.pdf] **PEER REVIEWED**
  • LD50 Zebrafish embryo 7.5 uM (24 hr); LD50 Zebrafish larvae 5 uM (24 hr)[Wu JY et al; Biol Pharm Bull 30 (7): 1336-9 (2007)] **PEER REVIEWED** PubMed Abstract

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Absorption, Distribution And Excretion

  • ...However, curcumin has a low systemic bioavailability, so it is imperative to improve the bioavailability of curcumin in its clinical application. Many methods, such as adjuvant drug delivery system and structural modification have been demonstrated to have a potential effect.[Fan X et al; Curr Pharm Des 19 (11): 2011-31 (2013)] **PEER REVIEWED** PubMed Abstract
  • Fifteen patients with advanced colorectal cancer received an extract of Curcuma (18 mg of diferuloylmethane and 2 mg of the desmethoxy derivative suspended in 200 mg of essential oils derived from Curcuma spp.) daily for up to 4 months. The doses were equivalent to 26, 72, 108, 144 and 180 mg of curcumin, with three patients receiving each dose. Neither diferuloylmethane, or its glucuronide or sulphate conjugates, or hexahydrocurcumin or hexahydrocurcuminol were detected in plasma or urine after up to 29 days of treatment. Diferuloylmethane was detected in the feces of all patients. Diferuloylmethane sulphate was also detected in the feces of one of the patients receiving diferuloylmethane at a dose of 180 mg/day, which may have been a result of biotransformation in the gut.[WHO ; WHO Food Additives Series 52 Curcumin (addendum); Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v52je04.htm] **PEER REVIEWED**
  • Oral & ip doses of (3)H-curcumin led to fecal excretion of most of radioactivity. Iv & ip doses were well excreted in bile of cannulated rats.[HOLDER ET AL; XENOBIOTICA 8(12) 761 (1978)] **PEER REVIEWED**
  • The aim of this study was to develop a curcumin intranasal thermosensitive hydrogel and to improve its brain targeting efficiency. The hydrogel gelation temperature, gelation time, drug release and mucociliary toxicity characteristics as well as the nose-to-brain transport in the rat model were evaluated. The developed nasal hydrogel, composed of Pluronic F127 and Poloxamer 188, had shorter gelation time, longer mucociliary transport time and produced prolonged curcumin retention in the rat nasal cavity at body temperature. The hydrogel release mechanism was diffusion-controlled drug release, evaluated by the dialysis membrane method, but dissolution-controlled release when evaluated by the membraneless method. A mucociliary toxicity study revealed that the hydrogel maintained nasal mucosal integrity until 14 days after application. The drug-targeting efficiencies for the drug in the cerebrum, cerebellum, hippocampus and olfactory bulb after intranasal administration of the curcumin hydrogel were 1.82, 2.05, 2.07 and 1.51 times that after intravenous administration of the curcumin solution injection, respectively, indicating that the hydrogel significantly increased the distribution of curcumin into the rat brain tissue, especially into the cerebellum and hippocampus. A thermosensitive curcumin nasal gel was developed with favourable gelation, release properties, biological safety and enhanced brain-uptake efficiency. /Curcumin intranasal thermosensitive hydrogel/[Chen X et al; J Pharm Pharmacol 65 (6): 807-16 (2013)] **PEER REVIEWED** PubMed Abstract
  • Twenty-five patients with conditions indicating a high risk of malignancy were given diferuloylmethane (purity, 99.3%) for 3 months. The starting dose was 500 mg/day, which was increased stepwise to 1000, 2000, 4000, 8000 and finally 12 000 mg/day. Pharmacokinetic studies were conducted in patients who agreed to give samples of blood and urine and in normal volunteers. Serum concentrations of diferuloylmethane peaked at 1-2 hr after administration of 4000-8000 mg diferuloylmethane and gradually declined within 12 hr. A half-life was not determined. Diferuloylmethane was barely detectable in the serum of patients taking 500-2000 mg of diferuloylmethane. No diferuloylmethane could be detected in urine. Similar results were obtained in two patients who had taken diferuloylmethane for more than 1 month, indicating that repeated administration did not alter the pharmacokinetic profile of this substance.[WHO ; WHO Food Additives Series 52 Curcumin (addendum); Available from, as of November 6, 2013: http://www.inchem.org/documents/jecfa/jecmono/v52je04.htm] **PEER REVIEWED**
  • When admin orally in dose of 1 g/kg, curcumin was excreted in feces to about 75%, while negligible amt appeared in urine. Measurement of blood plasma levels & biliary excretion showed that curcumin was poorly absorbed from the gut.[WAHLSTROM B, BLENNOW G; ACTA PHARMACOL TOXICOL 43(2) 86 (1978)] **PEER REVIEWED**

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Metabolism/Metabolites

  • Iv & ip doses of (3)H-curcumin excreted in bile of cannulated rats. Major metab were glucuronides of tetrahydrocurcumin & hexahydrocurcumin. Minor metab was dihydroferulic acid together with traces of ferulic acid.[HOLDER ET AL; XENOBIOTICA 8(12) 761 (1978)] **PEER REVIEWED**

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Tsca Test Submissions

  • None found

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Footnotes

1 Source: the NTP's CEBS database.

2 Source: the National Library of Medicine's Hazardous Substance Database, 02/28/2017.

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