SAFRANAL

SYNONYMS 

SAFRANAL 

(2,6,6-Trimethylcyclohexa-1,3-dienyl)methanal 

1,1,3-Trimethyl-2-formylcyclohexa-2,4-diene 

1,3-Cyclohexadiene-1-carboxaldehyde, 2,6,6-trimethyl- 

2,6,6-Trimethyl-1,3-cyclohexadienal 

2,6,6-Trimethylcyclohexa-1,3-dienyl methanal 

Dehydro-beta-cyclocitral 

Safranal 

CHEMICAL STRUCTURE 

CHEMICAL FORMULA 

C10H14O 

IDENTIFIER DETAILS 

CAS Number : 116-26-7 

CoE Number : 

FEMA : 3389 

EINECS Number : 204-133-7 

E Number : - 

SPECIFICATIONS 

Melting Point:

PURPOSE 

Flavouring substance. 

STATUS IN FOOD AND DRUG LAWS 

CoE limits: (Provisional) 

Beverages (ppm) Food (ppm) Exceptions (ppm) 

- - - 

Acceptable Daily Intake: 

ADI (mg/kg) ADI Set by Date Set Comments 

- - - - 

FDA Status:[CFR21] 

Section Number Comments 

- - 

HUMAN EXPOSURE 

Natural Occurrence: Safranal is reportedly found as a glucoside in saffron. 

Also reportedly found in grapefruit juice, saffron, black tea, green tea, 

bourbon, lemon, and sweet grass oil (Fenaroli, 2005) 

Reported Uses: Safranal is reportedly use in baked goods at 10ppm, 

condiments at 5 ppm, jams at 10 ppm and soft candy at 5 ppm (Fenaroli, 

2005) 

TOXICITY DATA 

In vivo Toxicity Status 

Carcinogenicity and Mutagenicity 

In a study conducted by Hariri et al., (2011), the effect of crocin and safranal 

was studied against subacute toxicity of diazinon (DZN) on hematological and 

genotoxicity indices in rats. The rats were divided into 16 groups consisted of 

6 rats in control, diazinon, vitamin E, vitamin E and DZN, crocin (3 doses), 

crocin (3 doses) and DZN, safranal (3 doses), safranal (3 doses) and DZN 

groups. Vitamin E (200 IU/kg), safranal at doses 0.025, 0.05 and 0.1 ml/kg 

and crocin at doses 50, 100 and 200 mg/kg were injected intraperitoneally to 

rats three times per week alone or with DZN (20 mg/kg/day, orally) for 4 

weeks. Hematological parameters were evaluated at the end of 4 weeks. The 

evaluation of genotoxicity was done using the micronucleus assay. Vitamin E 

and, at lower doses, safranal (0.025 and 0.05 ml/kg) and crocin (50 mg/kg) 

restored the reduction of red blood cell, hemoglobin and hematocrit indices 

induced by DZN. These agents at some doses also prevented the reduction in 

platelets counts indices in diazinon treated group. A significant increase in 

reticulocyte was induced by diazinon. Vitamin E, safranal (0.025 or 0.05 

Safranal.doc Page 2 of 5 August 2011

ml/kg) and all doses of crocin decreased this effect of diazinon. In all doses 

vitamin E, crocin and safranal did not inhibit the effect of diazinon on RBC 

cholinesterase activity. A significant increase in micronucleus indices was 

seen with diazinon. Vitamin E, safranal and crocin could not prevent this 

genotoxicity. This study showed that vitamin E, safranal and crocin (without 

effects on cholinesterase) reduced diazinon hematological toxicity, but they 

did not prevent the genotoxicity induced by diazinon. 

Dermal toxicity 

No data identified. 

Inhalation toxicity 


Reproductive and developmental toxicity 

In a study conducted by Hosseinzadeh et al., (2008), the aphrodisiac activities 

of Crocus sativus stigma aqueous extract and its constituents, safranal and 

crocin, were evaluated in male rats. The aqueous extract (80, 160 and 

320mg/kg body wt.), crocin (100, 200 and 400mg/kg body wt.), safranal (0.1, 

0.2 and 0.4ml/kg), sildenafil (60mg/kg body wt., as a positive control) and 

saline were administered intraperitoneally to male rats. Mounting frequency 

(MF), intromission frequency (IF), erection frequency (EF), mount latency 

(ML), intromission latency (IL) and ejaculation latency (EL) were the factors 

evaluated during the sexual behavior study. Crocin, at all doses, and the 

extract, especially at doses 160 and 320mg/kg body wt., increased MF, IF and 

EF behaviors and reduced EL, IL and ML parameters. Safranal did not show 

aphrodisiac effects. The present study reveals an aphrodisiac activity of 

saffron aqueous extract and its constituent crocin. 

Other relevant studies 


Behavioural data 


In Vitro Toxicity Status 

Carcinogenicity and mutagenicity 

The mutagenicity of the smoke condensate was assayed in the Salmonella 

plate incorporation [Ames] assay with the tester strain TA98 in the presence of 

an S9 metabolic activation system. The cytotoxicity of the cigarette 

condensate was determined in the neutral red uptake assay and the (3-(4,5dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H 

tetrazolium, inner salt assay (MTS assay) with the human hepatocellular liver 


carcinoma cell line, HEP-G2. It was concluded that the in vitro mutagenicity 

and cytotoxicity of the cigarette smoke was not increased by the addition of 

the ingredients, which included Safranal at levels up to 15 ppm. 

Extracts of saffron (Crocus sativus L.) have been reported to inhibit cell 

growth of human tumor cells. In order to study the cytotoxic effect of the 

characteristic compounds of saffron spice, Escribano et al., (1996) isolated 

crocin, crocetin, picrocrocin and safranal. Doses inducing 50% cell growth 

inhibition (LD50) on HeLa cells were 2.3 mg/ml for an ethanolic extract of 

saffron dry stigmas, 3 mM for crocin, 0.8 mM for safranal and 3 mM for 

picrocrocin. Crocetin did not show cytotoxic effect. Cells treated with crocin 

exhibited wide cytoplasmic vacuole-like areas, reduced cytoplasm, cell 

shrinkage and pyknotic nuclei, suggesting apoptosis induction. Considering its 

water-solubility and high inhibitory growth effect, crocin is the more promising 

saffron compound to be assayed as a cancer therapeutic agent. 

The influence of safranal, a constituent of Crocus sativus L. stigmas, on 

methyl methanesulfonate (MMS)-induced DNA damage was examined using 

alkaline single-cell gel electrophoresis (SCGE), or comet, assay in multiple 

organs of mice (liver, lung, kidney, and spleen) by Hosseinzadeh et al., 

(2007). NMRI mice were divided into five groups, each of which contained five 

mice. The animals in different groups were received the following chemicals: 

physiological saline (10 mL/kg, ip), safranal (363.75 mg/kg, ip), MMS (120 

mg/kg, ip), safranal (72.75 mg/kg, ip) 45 min prior to MMS administration, and 

safranal (363.75 mg/kg, ip) 45 min prior to MMS administration. Mice were 

sacrificed about 3 h after the administration of direct mutagen MMS, safranal, 

or saline, and the alkaline comet assay was used to evaluate the influence of 

safranal on DNA damage in different mouse organs. Increase in DNA 

migration was varied between 9.08 times (for spleen) and 22.12 times (for 

liver) in nuclei of different organs of MMS-treated mice, as compared with 

those of saline-treated animals (p < 0.001). In control groups, no significant 

difference was found in the DNA migration between safranal- and salinepretreated 

mice. The MMS-induced DNA migration in safranal-pretreated mice 

(363.75 mg/kg) was reduced between 4.54-fold (kidney) and 7.31-fold (liver) 

as compared with those of MMS-treated animals alone (p < 0.001). This 

suppression of DNA damage by safranal was found to be depended on the 

dose, and pretreatment with safranal (72.75 mg/kg) only reduced DNA 

damage by 25.29%, 21.58%, 31.32%, and 25.88% in liver, lung, kidney, and 

spleen, respectively (p < 0.001 as compared with saline-treated group). The 

results of the present study showed that safranal clearly repressed the 

genotoxic potency of MMS, as measured by the comet assay, in different 

mouse organs, but the mechanism of this protection needs to be more 

investigated using different in vitro system assays and different experimental 

designs. 

REFERENCES 

Escribano J, Alonso GL, Coca-Prados M, Fernandez JA. (1996). Crocin, 

safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of 

human cancer cells in vitro. Cancer Lett. 100(1-2):23-30. [Cancer letters] 


Fenaroli (2005) Fenaroli's Handbook of Flavor Ingredients, 5th Edition, CRC 

Press, London. 

Hariri AT, Moallem SA, Mahmoudi M, Hosseinzadeh H. (2011). The effect of 

crocin and safranal, constituents of saffron, against subacute effect of 

diazinon on hematological and genotoxicity indices in rats. Phytomedicine. 

15;18(6):499-504. 

Hosseinzadeh H, Sadeghnia HR (2007). Effect of safranal, a constituent of 

Crocus sativus (saffron), on methyl methanesulfonate (MMS)-induced DNA 

damage in mouse organs: an alkaline single-cell gel electrophoresis (comet) 

assay. DNA Cell Biol. 26(12):841-6. [DNA and cell biology] 

Hosseinzadeh H, Ziaee T, Sadeghi A. (2008). The effect of saffron, Crocus 

sativus stigma, extract and its constituents, safranal and crocin on sexual 

behaviors in normal male rats. Phytomedicine. 2008, Jun; 15(6-7):491-5.

SAFRANAL

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