Copyright © 2014 Ramesh Edamula et al. This is an open access article distributed under the Creative Commons Attribution License , which per- mits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. International Journal of Pharmacology and Toxicology, 2 (2) (2014) 46-49 International Journal of Pharmacology and Toxicology Journal home page: www.sciencepubco.com/index.php/IJPT doi: 10.14419/ijpt.v2i2.3035 Research Paper Prenatal Developmental Toxicity of Crocus sativus (saffron) in Wistar rats Ramesh Edamula 1 *, M.Deecaraman 2 , D.P.Santhosh Kumar 1 , H.N.Krishnamurthy 1 , M.Latha 1 1 Department of Safety Assessment, Advinus Therapeutics Limited, Peenya II Phase, Bangalore – 560 058, India 2 Department of Biotechnology, Dr.M.G.R Educational and Research Institute, Maduravoyal, Chennai - 600 095, India *Corresponding author E-mail: edamularamesh@gmail.com Abstract The prenatal developmental toxicity of Crocus sativus (saffron) was evaluated in a mammalian species taking Wistar rat as the model. Saffron administered as an oral gavage from Day 5 of gestation (day of implantation) until Day 19 of gestation at the doses of 50, 250 and 1000 mg/kg/day did not elicit any effects on maternal body weight gains, food intake, gravid uterine weight, corpora lutea and im- plantation counts, pre and post implantation loss, litter size, weight and length. No abnormalities in the fetuses were noticed when sub- jected to external, soft tissue and skeletal examinations. The results obtained conclude that saffron did not induce maternal toxicity and structural and / or other abnormalities in the fetus and hence saffron is considered to have no teratogenic potential. Keywords: Abnormalities, Fetus, Litter, Saffron, Skeletal. 1. Introduction Crocus sativus is an herbaceous perennial cormous plant belong- ing to family Iridacea and is commonly known as saffron. Saffron contains more than 150 volatile and aroma yielding compounds. The value of saffron is determined by the existence of three main metabolites – Crocin and its derivatives which are responsible for colour, Picrocrocin responsible for the bitter taste and Safranal responsible for the odour/aroma. The flower styles which are what basically form commercial saffron used by most people either for medicinal or culinary purposes. It has been reported that saffron has anti-inflammatory, antidiabetic, anticancer, hypolipaemic, anti-spasmodic or anti-seizure, expectorant effects. It is also a protective agent against chromosomal damage, a modulator of lipid peroxidation, for reducing blood pressure and also used in treatment of psoriasis (Bhargava 2011). In contrary to beneficial effect, information related to saffron toxicity has also appeared (HosseinZadeh et al. 2013). Crocetin, a carotenoid isolated from saffron has been found to be a teratogen (Martin et al. 2002). At low doses, saffron causes the stimulation of the pregnant uterus and in larger amounts can cause contraction and spasm leading to abortion and possible toxic symptoms. Although generally saffron is considered to be safe, it was decided to evaluate the effect of saffron on embryo fetal developmental toxicity (teratogenicity) potential to induce structural and /or other abnormalities in the fetuses when administered orally to pregnant rats during gestation days 5 through 19. 2. Material and methods 2.1. Saffron Saffron (stigma of flower) was obtained from Indian Saffron In- dustry, Bagander, Pampore, Kashmir – 192121, India. The ob- tained material was authenticated by means of a spectrophotomet- ric method based on International Organization for Standardiza- tion (ISO) 5453, Part II, 1996 at Central Food Technological Re- search Institute, Mysore-570020, India and a test report provided by the analyzer. The results indicated that the three main compo- nents present in the material on dry basis were: Picrocrocin – 72.7 %, Safranal – 51.6 % and colouring strength – 142.5 %. No added artificial colour was present in the material. 2.2. Animals and methodology Wistar rats, in-house bred at Department of Safety Assessment, Advinus Therapeutic Limited, Peenya Industrial Area, Bangalore – 560058, India were used in the experiment. 24 females con- firmed mated by vaginal smear examination with weight ranging from 185 to 238 grams and 11 to 12 weeks old were divided into 4 groups of 6 each and housed in a barrier facility with standard laboratory condition of 12 – 15 filtered fresh air changes, tempera- ture range of 20 to 23 °C, relative humidity of 30 to 70 % with 12 hours fluorescent light and 12 hours dark cycle and with free ac- cess to food and water. The experimental project was approved by the Institutional Animal Ethics Committee (Proposal No. 023, dated 21 March, 2012). 6 animals in Group I received only the vehicle (Milli-Q water) at 10 mL/kg body weight through oral gavage. The 6 animals each in Group II, Group III and Group IV received saffron suspended in Milli-Q water at the doses of 50 mg/kg/day, 250 mg/kg/day and 1000 mg/kg/day, respectively at 10 mL/kg body weight through oral gavage. All the presumed pregnant females were continuously dosed from Day 5 of gestation (day of implantation) until Day 19 of gestation. Animals were weighed on specified intervals and food intake was also measured. Daily records of activity with reference to appearance and behavior were maintained.