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. 2020 Jun 12;18(6):e06146. doi: 10.2903/j.efsa.2020.6146
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