Acute and Chronic Toxicity Study of Vatavidhvamsana Rasa, an Ayurvedic Herbomineral Formulation

Jump To References Section


  • Central Ayurveda Research Institute, Patiala, Punjab –147001 ,IN
  • Department of Rasasatra and Bhaishajya Kalpana, Institute of Teaching and Research in Ayurveda, Jamnagar – 361008, Gujarat ,IN
  • Pharmacology Department, Institute of Teaching and Research in Ayurveda, Jamnagar – 361008, Gujarat ,IN
  • Department of Rasasatra and Bhaishajya Kalpana, Institute of Teaching and Research in Ayurveda, Jamnagar – 361008, Gujarat ,IN



Acute Toxicity, Chronic Toxicity, Heavy Metal Toxicity, Herbominerals, Vatavidhvamsana Rasa


Vatavidhvamsana Rasa (VVR)is a famous herbomineral formulation containing various processed metals, minerals and herbals and is mainly used in treating neurological and muscular diseases. Herbomineral formulations in Ayurveda are always under scrutiny for safety aspects due to the presence of heavy metals. This study is an attempt to evaluate the safety of Vatavidhvamsana Rasa through acute toxicity and 90 days repeated dose toxicity. The oral acute toxicity study of VVR was accomplished in Wistar albino rats at a limit dose of 2000 mg/ kg. The oral repeated dose toxicity study (90 days) of VVR was carried out by administering VVR with honey at therapeutically equivalent dose (22.5 mg/kg), TEDx5 (112.5 mg/kg) and TEDx10 (225 mg/kg) dose levels. One recovery group (225 mg/kg) was kept for observation for 30 days after the treatment period. Vatavidhvamsana Rasa did not produce any observable toxic effects during acute toxicity study. There were also no significant behavioural changes during the entire duration of the acute study and all animals survived during the 14 days of observation. This implicates that the LD50 value of Vatavidhvamsana Rasa would be more than 2000 mg/kg by oral route. In chronic toxicity study, Vatavidhvamsana Rasa with honey as adjuvant given at different dose levels had not produce any major adverse effects in albino rats during the study period of 90 days along with a recovery period of 30 days. VVR at higher dose showed no significant changes in histopathology, hematological and serum biochemical parameters. At higher dose level of VVR at TEDx10 for 90 days, drug has potential to produce changes in liver and kidney related parameters. From the above data, it can be concluded that VVR with honey administered orally in rats was found to be safe in acute toxicity study and also at therapeutic dose level during chronic toxicity study in albino rats.


Download data is not yet available.



How to Cite

Mahesh, S., Chaudhary, S. Y., Nariya, M., & Patgiri, B. J. (2021). Acute and Chronic Toxicity Study of <i>Vatavidhvamsana Rasa</i>, an Ayurvedic Herbomineral Formulation. Toxicology International, 28(4), 421–433.



Original Research
Received 2021-07-09
Accepted 2021-08-10
Published 2021-12-22



Ernst E. Toxic heavy metals and undeclared drugs in Asian herbal medicines. Trends Pharmacol Sci. 2002; 23(3):136–9. PMID: 11879681. DOI:

Kumar A, Nair AG, Reddy AV, Garg AN. Bhasmas: unique ayurvedic metallic-herbal preparations, chemical characterization. Biol Trace Elem Res. 2006; 109(3):231–54. PMID: 16632893. DOI:

Saper RB, Phillips RS, Sehgal A, Khouri N, Davis RB, Paquin J, Thuppil V, Kales SN. Lead, mercury, and arsenic in US and Indian-manufactured Ayurvedic medicines sold via the Internet. JAMA. 2008; 300(8):915–23. Erratum in: JAMA. 2008; 300(14):1652. PMID: 18728265. PMid:18728265 PMCid:PMC2755247. 00.8.915 DOI:

Cooper K, Noller B, Connell D, Sadler R, Olszow H, Golding G et al. Public health risks from heavy metals and metalloids. Journal of Toxicology and Environmental Health. 2007;70:1694–9. PMid:17763088. 01434885 DOI:

Kumar, A, Garg, AN, Nair AGC, Reddy AVR. Availability of essential elements in bhasmas. Analysis of Ayurvedic metallic preparations by INAA. Hungary. DOI:

Chan K. Some aspects of toxic contaminants in herbal medicines. Chemosphere. 2003; 52(9):1361–71. PMID: 12867165. DOI:

Mukherjee PK, Harwansh RK, Bahadur S, Banerjee S, Kar A, Chanda J, Biswas S, Ahmmed SM, Katiyar CK. Development of Ayurveda - Tradition to trend. J Ethnopharmacol. 2017; 197:10–24. Epub 2016 Sep 12. PMID: 27633405. DOI:

Kushwaha H., editor. Charaka, Charaka Samhita, Chaukhamba Orientalia, Varanasi; 2010.

Kamath SU, Pemiah B, Sekar RK, Krishnaswamy S, Sethuraman S, Krishnan UM. Mercurybased traditional herbo-metallic preparations: A toxicological perspective. Arch Toxicol. 2012; 86(6):831–8. Epub 2012 Mar 23. PMID: 22441626. DOI:

Krishnamachary B, Rajendran N, Pemiah B, Krishnaswamy S, Krishnan UM, Sethuraman S, Sekar RK. Scientific validation of the different purification steps involved in the preparation of an Indian Ayurvedic medicine, Lauhabhasma. J Ethnopharmacol. 2012; 142(1):98–104. Epub 2012 Apr 26. PMID: 22561344. DOI:

Kohli KR. Ayurvedic medicines and heavy metals issue. Ayurveda Herit 2005; 1:5–6.

Chauhan P. Ayurvedic Metallic Medicines are NOT FATAL (Part 1 to 3). Ayurveda for you. 2019. http:// html

Chandra S. Ayurvedic research, wellness and consumer rights. J Ayurveda Integr Med. 2016; 7(1):6–10. Epub 2016 May 25. PMID: 27297503; PMCID: PMC4910573. DOI:

Dwivedi V, Anandan EM, Mony RS, Muraleedharan TS, Valiathan MS, Mutsuddi M, Lakhotia SC. In Vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster Model Relate with Therapeutic Applications. Journal. PLOS. 2012; 7(5):1–14. PMid:22606337 PMCid:PMC3351451. DOI:

Tripathi I, Sastri VL. Yogaratnakara. Varanasi: Chaukamba Krishnadas Academy; 1998.

Anonymous. The Ayurvedic Formulary of India. 1st ed. The Ministry of Health and Family Welfare, Dept. of Indian systems of Medicine and Homoeopathy, Part II. New Delhi: 2000.

Vaghabhata. Rasaratna Samuchaya. Varanasi: Chaukhambha Sanskrit Sansthan; 2012.

Krishnarama B, Manimala S. Varanasi: Chaukhamba Krishndas Academy; 2008.

Shastri K (Ed.), Sharma S, Rasatarangini. Delhi: Motilal Banarasidas Publication; 2009.

Paget GE, Branes JM. Toxicity tests. Laurence DR, Bocharach AL, Eds. Evaluation of drug activities: Pharmacometrics. New York: Academic Press; 1964. DOI:

OECD (2008), Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, DOI:

OECD (2018), Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, DOI:

Pennock CA, Murphy D, Sellers J, Longdon KJ. A comparison of autoanalyser methods for the estimation of glucose in blood. Clin Chim Acta. 1973; 48(2):193–201. PMID: 4758882. https://doi. org/10.1016/0009-8981(73)90365-3 DOI:

Roeschlau P, Bernt E, Gruber W. Enzymatic determination of total cholesterol in serum. Z Klin Chem KlinBiochem. 1974; 12(5):226. PMID: 4440114.

McGowan MW, Artiss JD, Strandbergh DR, Zak B. A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem. 1983; 29(3):538–42. PMID: 6825269. https://doi. org/10.1093/clinchem/29.3.538 DOI:

Tiffany TO, Jansen JM, Burtis CA, Overton JB, Scott CD. Enzymatic kinetic rate and end-point analyses of substrate, by use of a GeMSAEC fast analyzer. Clin Chem. 1972; 18(8):829–40. PMID: 5043271. DOI:

Slot C. Plasma creatinine determination. A new and specific Jaffe reaction method. Scand J Clin Lab Invest. 1965; 17(4):381–7. PMID: 583827 DOI:

Bradley DW, Maynard JE, Emery G, Webster H. Transaminase activities in serum of long-term hemodialysis patients. Clin Chem. 1972;18(11):1442. PMID: 4652847. 11.1442b DOI:

Gowda S, Desai PB, Hull VV, Math AA, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J. 2009; 3:17. PMID: 21532726; PMCID: PMC2984286.

Tietz NW. editor. Text book of Clinical Chemistry. Philadelphia: WB Saunders and Company. 1986; 579. DOI:

Doumas BT, Arends RL, Pinto PC in standard methods of clinical chemistry. Academic Press Chicago. 1972; 7:175–89. DOI:

Wilkinson JH, Boutwell JH, Winsten S. Evaluation of a new system for the kinetic measurement of serum alkaline phosphatase. Clin Chem. 1969; 15(6):487– 95. PMID: 5786804. DOI:

Pearlman FC, Lee RT. Detection and measurement of total bilirubin in serum, with use of surfactants as solubilizing agents. Clin Chem. 1974; 20(4):447– 53. PMID: 4818198. DOI:

Burtis CA, Ashwood ER, Eds. Tietz Textbook of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders. 1999; 1136.

Kabasakalian P, Kalliney S, Westcott A. Determination of uric acid in serum, with use of uricase and a tribromophenol-aminoantipyrine chromogen. Clin Chem. 1973; 19(5):522–4. PMID: 4703662. DOI:

Moorehead WR, Biggs HG. 2-Amino-2-methyl- 1-propanol as the alkalizing agent in an improved continuous-flow cresolphthalein complexone procedure for calcium in serum. Clin Chem. 1974; 20(11):1458–60. PMID: 4421368. DOI:

Raghuramulu N, Nair KM, Kalyanasundaram S. (Ed). A Manual of Laboratory Techniques, National Institute of Nutrition (NIN) Hyderabad India; 1983. p. 246–53.

Mahesh S, Patgiri BJ, Praveen Kumar KS. A review on Vatavidhvamsana Rasa, An Ayurvedic Herbomineral Preparation. Int. J. Res. Ayurveda Pharm. 2020; 11(4):143–6 DOI:

Mahesh S, Patgiri BJ. Praveen Kumar KS. Pharmaceutico-analytical study of Vatavidhvamsana Rasa. International Journal of Ayurvedic Medicine. 2020; 11(2):235–40. DOI:

Lipnick RL, Cotruvo JA, Hill RN, Bruce RD, Stitzel KA, Walker AP, Chu I, Goddard M, Segal L, Springer JA, et al. Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures. Food Chem Toxicol. 1995; 33(3):223–31. PMID: 7896233. DOI:

Timbrell JA. Principles of Biochemical toxicology. Taylor and Francis Ltd., London; 1982.

Anonymous. Class 6-toxic and infectious substances. UN recommendations on the transport of dangerous goods-model regulations. Part-2. 12th revised ed. Ch. 2.6. Geneva: United Nations Publications; 2001.

Heywood, “Long term toxicity,” in Animals and Alternatives in Toxicity Testing, M. Balls, R. J. Riddell, and A. N. Worden, Eds., Academic Press, London, UK;1983.

Nikolic R, Krstic N, Jovanovic J, Kocic G, Cvetkovic TP, Radosavljevic-Stevanovic N. Monitoring the toxic effects of Pb, Cd and Cu on hematological parameters of Wistar rats and potential protective role of lipoic acid and glutathione. Toxicol Ind Health. 2015; 31(3):239–46. Epub 2013 Jan 4. PMID: 23293128. DOI:

Khan AR, Awan FR. Metals in the pathogenesis of type 2 diabetes. J Diabetes MetabDisord. 2014;13(1):16. PMID: 24401367; PMCID: PMC3916582. DOI:

Rice KM, Walker EM Jr, Wu M, Gillette C, Blough ER. Environmental mercury and its toxic effects. J Prev Med Public Health. 2014; 47(2):74–83. PMid:24744824 PMCid:PMC3988285. DOI:

Philips CA, Paramaguru R, Augustine P. Ayurveda metallic-mineral ‘Bhasma’-associated severe liver injury. BMJ Case Rep. 2018. PMid:29960971 PMCid:PMC6040517. DOI:

Satyanarayana U, Chakrapani U. Biochemistry. 4th ed. Elsevier: New Delhi; 2013.

Amin A, Hamza AA. Oxidative stress mediates druginduced hepatotoxicity in rats: A possible role of DNA fragmentation. Toxicology. 2005; 208(3):367– 75. PMID: 15695022. DOI:

Pachathundikandi SK, Varghese ET. Blood zinc protoporphyrin, serum total protein and total cholesterol levels in automobile workshop workers in relation to lead toxicity: Our experience. Indian J Clin Biochem. 2006; 21(2):114–7. PMid:23105626 PMCid:PMC3453998. DOI:

Gad SC. The rat: Pathology. Gad SC, Chengellis CP.Eds. Animal Models in Toxicology. New York: Marcel Dekker; 1992. p.478. DOI: