Type of test | Experimental test system (aim of the study) | Test substance/relevance | Exposure conditions | Result | Comments/Reliability | Relevance of the results |
---|---|---|---|---|---|---|
Aggarwal et al. (2016) |
BM cells of Swiss albino mice, 8–12 weeks old Males+Females (10M + 10F per group, 3 groups, one treated group, negative and positive controls Parallel 90‐day toxicity study in males and female rats (OECD no. 480). Maximal Tolerates Dose, Minimal Lethal Dose and LD50: > 5,000 mg/kg bw |
Curcuminoids‐essential oil complex (CEC, with 95% curcuminoid complex, India), with increased bioavailability Relevance: high Negative control: corn oil (oral) Positive control: CP (i.p., 40 mg/kg bw, sampling: 24 h) |
2,000 mg CEC/kg bw (max tolerated dose), oral administration Sampling time: 24 and 48 h after administration (5M+5F per time point) 200 erythrocytes/slide counted for % PCE; 2,000 PCE/animal scored for MN |
No mortality, no signs of toxicity Positive controls: stat. signif. increase in the number of MNPCE No statistical increase in frequency of MN PCE No effect on PCE/NCE (no cytotoxicity) Acute toxicity: no clinical signs of toxicity at the dose of 5,000 mg/kg bw Negative |
OECD 474 not mentioned, but compliant Reliable with minor restrictions Only one dose tested Historical data not provided No indication if BM was exposed The compound was tested up to the highest recommended dose by OECD TG 474 |
Limited |
Çelik et al. (2013) |
BM cells of Swiss albino rats (Wistar rats), 6–8 weeks old Females (9 groups of 6 rats) curcumin treated group; 3 PFOS treated groups, 3 PFOS + Curcumin treated groups, negative and positive controls Aim of the study: modulation on effects of perfluorooctane sulfonate (PFOS) |
Curcumin (Sigma Aldrich purity > 99%) Relevance: high Negative control: Vehicle: saline Positive control: MMC (i.p., single dose 2 mg/kg at the 16th week) |
80 mg/kg bw curcumin by gavage for 30 days at 48 h intervals, sacrificed 30 h after last treatment 200 erythrocytes/animal for % PCE; 2,000 PCE/animal scored for MN |
Positive controls: stat. signif. increase in the number of MNPCE No stat. signif. increase in the MN frequency by curcumin Dose‐related increase of MN frequency by PFOS alone and also in combination with curcumin No decrease in PCE/200 TE by curcumin alone Negative |
Procedure described by Schmidt (1993) and Agarwal (1994) Reliable with restrictions Only one dose tested Highest dose tested below OECD recommendations Historical data not provided No indication if BM was exposed |
Low |
Damarla et al. (2018) |
BM cells of Swiss albino mice, 7–9 weeks old Males+Females (5M+5F per group, 5 groups, 3 treated, negative and positive controls |
Synthetic curcumin (99.4% purity) Relevance: high Negative control: Vehicle: 0.5% w/v CMC Positive control: CP (30 mg/kg bw, single dose, gavage, sampling 24 h) |
0, 500, 1,000 and 2,000 mg/kg bw, by gavage, for 2 consecutive days Sampling time: 24 after second administration 500 erythrocytes/ animal scored; 4,000 PCE/animals scored for MN |
No mortality, no signs of toxicity Positive controls: stat. signif. increase in the number of MNPCE Negative controls: within historical control laboratory values No statistical signif. increase in frequency of MN PCE No effect on PCE/TE Negative |
GLP compliant According to OECD 474 (2014) Reliable with minor restrictions No indication if BM was exposed The compound was tested up to the highest recommended dose by OECD TG 474 |
Limited |
Dandekar et al., 2010a; |
BM cells of Swiss albino mice, 6–8 weeks old Males+Females (n = 10, M/F 5/5 each group) Six groups:3 treated groups, Negative and positive controls Parallel acute (2,000 mg/kg bw per kg and sub‐acute (28 d, up to 200 mg/kg) toxicity studies in males and female rats (OECD, 1996, 1995, as referenced by Dandekar et al. (2010a) no. 425 and 407): no signs of toxicity |
Curcumin nanoparticles (NP) of Eudragit® S100 Relevance: limited Negative control: Vehicle: distilled water Blank nanoparticles Positive control: CP (40 mg/kg bw) |
Four curcumin NP doses tested, corresponding to 0 (blank NP), 100, 200 and 300 mg/kg bw (gavage), administration once daily on 2 consecutive days; sampling at the end of treatment 2,000 erythrocytes per animal; PCE and NCE scored |
Positive controls: stat. signif. increase in the number of MNPCE and decrease in PCE/NCE No stat. signif increase in frequency of MN PCE No effect on PCE/NCE (no cytotoxicity) Negative |
OECD not mentioned Reliable with restrictions Highest dose tested below OECD recommendations Historical data not provided No indication if BM was exposed |
Low |
Dandekar et al. (2010b) |
BM cells of Swiss albino mice Males+Females (5M/5F per group, six groups) Parallel acute (2,000 mg/kg bw per kg and sub‐acute (28 d, up to 200 mg/kg) toxicity studies in males and female rats (see above) |
Hydrogel nanoparticles (NP) of curcumin (95%) based on HPMC and PVP Relevance: limited Negative control: Vehicle: distilled water Positive control: CP (40 mg/kg bw) |
Four curcumin NP doses tested, corresponding to o (blank NP), 100, 200 and 300 mg/kg bw (gavage), administration once daily on 2 consecutive days; sampling at the end of treatment 2,000 erythrocytes per animal; PCE and NCE scored |
Positive controls: stat. signif. increase in the number of MNPCE and decrease in PCE/NCE No stat. signif increase in frequency of MN PCE No effect on PCE/NCE (no cytotoxicity) Negative |
OECD not mentioned Reliable with restrictions Highest dose tested below OECD recommendations Historical data not provided No indication if BM was exposed |
Low |
El‐Makawy and Sharaf (2006) |
BM cells of Wistar rats Males (10/group) 7 groups: 5 treated groups, negative and positive controls |
Curcumin spice (not characterised) Relevance: very low Negative control: Vehicle: distilled water Positive control: CP (25 mg/kg bw, i.p., single dose) |
Five doses tested, 0.5, 5, 10, 25 and 50 mg/kg bw, daily oral administration for 4 weeks Sampling 24 h after last administration 2,000 PCE/animal scored for MN |
Positive controls: stat. signif. increase in the number of MNPCE Curcumin caused a significant dose‐dependent increase of MNPCE, significant at doses ≥ 5 mg/kg bw No data on PCE/NCE Positive |
OECD not mentioned Reliable with restrictions Highest dose tested below OECD recommendations Historical data not provided No bone marrow exposure Evaluated by EFSA 2010 as positive, but the Panel noted that the curcumin tested was not adequately specified |
Very low |
Farag et al., 2014; |
Whole blood of chickens 6 groups: 2 turmeric groups, endosulfan group, 2 endosulfan+ turmeric groups, negative controls, Also tested in combination with endosulfan (protective effects of turmeric) |
Turmeric (Curcuma longa) Relevance: limited Negative control:normal diet Positive control: endosulfan (30 mg/kg) |
Doses tested: 5 and 10 mg turmeric/kg diet, for 5 weeks 1,000 erythrocytes/group scored for MN |
No stat. signif increase in frequency of MN induced by turmeric Endosulfan increased MN, decreased by co‐exposure to turmeric Negative |
Historical data not provided Not reliable in vivo MN not validated in chicken, experimental protocol not standardised |
None |
Farhadi et al. (2018) |
Human blood samples 21 patients with differentiated thyroid carcinoma, 11 (6F) patients receiving curcumin, 10 (5F) receiving placebo Aim of thestudy: Radioprotective effects against genotoxicity induced by Iodine‐131 |
Nano‐curcumin (nano micellar soft gel capsules) Relevance: limited |
Curcumin 160 mg/day, orally given from 3 days before to 7 days after 131I therapy blood sampling before treatment and 1 week after Phytohemagglutinin incubated at 37°C for 44 h Cytochalasin B Two paired cultures per sample At least 1,000 binucleated cells/per patient, before and after therapy |
Baseline MN same in patients receiving curcumin and placebo Treatment with 131I sign. increased MN After 1 week treatment with 131I, the frequency of MN decreased in patients receiving curcumin by 32% Negative |
Not relevant for the purpose of the assessment (biomonitoring study in a group of patients) |
None |
Jain et al. (1987) |
BM cells of mice (unspecified) Males (4 per group) |
Turmeric powder, dried methanolic extract (containing about 3% curcumin) Relevance: limited Negative control: Vehicle: DMSO Positive control: MMC (2 mg/kg bw, i.p., single dose) |
Doses tested: 100, 250 and 500 mg/kg bw, i.p., single dose, after 22 h, colchicine injected (0.2 mg/kg bw), animals sacrificed after 2 h At least 1,000 PCE/animal scored for MN |
Positive controls: stat. signif. increase in the number of MNPCE Statistical signif. increase in MN frequency at the dose 250 mg/kg bw No dose‐response No data on PCE/NCE Negative |
Not reliable Historical data not provided No indication if BM was exposed (No data on PCE/NCE) Evaluated by JECFA FAS 35 as negative |
Low |
Khatik et al. (2016 |
BM cells of Balb/c mice, 6‐8 week old 4 groups, 4 animals per group (two treated groups, Negative and positive controls |
Complexes (1:1) between curcumin phosphatidylcholine (CU‐PC) and hydrogenated soya PC (CU‐HSPC) Negative control: Vehicle: distilled water Positive control: CP (40 mg/kg bw) Relevance: limited |
One dose tested: 100 mg/kg bw of CU (as CU‐PC and CU‐HSPC), administration once daily on 2 consecutive days, gavage Sampling at the end of the treatment At least 1,000 PCE scored for the presence of MN |
Positive controls: stat. signif. increase in the number of MNPCE No statistical signif. increase in frequency of MN PCE and no effect on PCE/NCE by curcumin with both complexes Negative |
OECD not mentioned Reliable with restrictions Only one dose tested Highest dose tested below OECD recommendations Historical data not provided No indication if BM was exposed |
Low |
Mendonça et al. (2015) |
BM cells of Wistar albino Rats, 5–6 weeks old Males, 12 groups, 6 animals per treatment Aim of the study: modulation on effects induced by cisplatin (cDDP) |
Curcumin (CMN Sigma Aldrich purity > 99%) and curcumin solid dispersion (CMN SD) Relevance: high (CMN) Negative control: Saline solution and GLA (components used for SD) Positive control: Cisplatin (cDDP), 6 mg/kg bw CMN and CMN SD in combination with cDDP |
CMN 50 mg/kg bw and CMN SD 5, 25 and 50 mg/kg bw, by gavage at 72, 48, 24 h and 30 min before i.p. administration of saline or cDDP Three slides/animal PCE and NCE scored in 500 erythrocytes; 2,000 PCE per animal scored for MN Oxidative stress parameters also measured in kidney (TBARS, GSH, Tp53 gene expression levels) |
Positive controls: stat. signif. increase in the number of MN PCE No stat. signif. increase in frequency of MN PCE by curcumin in both forms CMN and CMN SD significantly decreased the formation of MN by cDDP Negative |
OECD not mentioned but probably in line Reliable with restrictions Only one CMN dose tested Highest dose tested below OECD recommendations Historical data not provided No direct indication if BM was exposed, but indirect evidence The study is of low relevance regarding for the genotoxicity of curcumin but provide some evidence of bioavailability of curcumin in relation to modulation of genotoxic effects of cisplatin |
Limited |
Ravikumar et al. (2018) |
BM cells of Wistar rats, 6–8 weeks old Males and females (5+5 per group) |
Curo White (Aurea Biolabs, Ltd., Kerala, India) 25–27% standardised hydrogenated curcumin powder (from turmeric rhizome powder by extraction, hydrogenation, encapsulation with beta‐cyclodextrin and spray drying) Relevance: limited Negative control: Vehicle: DMSO Positive control: CP (50 mg/kg bw, gavage) |
Three curcumin doses tested, 200, 400 and 800 mg/kg bw, administration once daily on 2 consecutive days, gavage Sampling time: 24 after second administration PCE and NCE scored in 200 erythrocytes; 2,000 PCE/animal scored for MN |
No mortality, no clinical signs of toxicity Positive controls: stat. signif. increase in the number of MNPCE Negative controls: within historical controls No stat. signif. increase in frequency of MN PCE No effect on PCE/NCE (no cytotoxicity) Negative |
GLP compliant According to OECD 474 (1997) Reliable with minor restrictions Highest dose tested below OECD recommendations No indication if BM was exposed |
Low |
Vijayalaxmi (1980) |
BM cells of Swiss albino mice Females (24), 3 groups, 8 animals per treatment 2 treated group (turmeric and curcumin) negative control group |
Turmeric and curcumin Relevance: limited Control: normal diet Positive control: none |
0.5% turmeric and 0.015% curcumin added to diet, for 12 weeks Sampling at the end of the study 2,000 PCE per animal scored for MN |
No stat. signif. increase in frequency of MN induced by turmeric and curcumin compared to control Negative |
OECD not mentioned Reliable with restrictions No positive controls Only one dose tested No indication if BM was exposed Evaluated by JECFA FAS 17 as negative |
Low |
Zheng et al. (2016) |
BM cells of Balb/c mice, 6–8 weeks old 5 groups, 4 animals per group |
Two types of chitosan nanoparticles (CNP) loaded with curcumin (release investigated) Relevance: limited Negative control: vehicle: distilled water Positive control: CP (40 mg/kg bw) |
One dose tested (40 mg/kg bw) of the two formulations, corresponding to 100 mg curcumin/kg (gavage), administration once daily on 2 consecutive days; sampling at the end of the study 1,000 PCE per animal scored for MN |
Positive controls: stat. signif. increase in the number of MN No stat. signif. increase in frequency of MN by curcumin in both forms Negative |
OECD not mentioned Reliable with restrictions Only one dose tested Highest dose tested below OECD recommendations Historical data not provided No indication if BM was exposed |
Low |