Safety Assessment of AYUSH SC-3 through Acute and 90 Days Repeated Dose Oral Toxicity Study

Jump To References Section

Authors

  • Sudesh N. Gaidhani
     Department of Pharmacology, National Ayurveda Research Institute Panchakarma, Cheruthuruthy, Thrissur - 679531, Kerala ,IN
  • S. Viswanth Reddy
     Department of Pharmacology, National Ayurveda Research Institute Panchakarma, Cheruthuruthy, Thrissur - 679531, Kerala ,IN
  • Srikanth Ala
     Department of Pharmacology, National Ayurveda Research Institute Panchakarma, Cheruthuruthy, Thrissur - 679531, Kerala ,IN
  • Sanjaya Kumar
     Central Council for Research in Ayurvedic Sciences, New Delhi - 110058, Delhi ,IN
  • Shrirang Jamadagni
     Regional Ayurveda Research Institute, Pune - 411038, Maharashtra ,IN
  • Pranita Joshi Deshmukh
     MAM’s Sumatibhai Shah Ayurved Mahavidyalaya, Pune - 411028, Maharashtra ,IN
  • K. Subrahmanyam
     Department of Pharmacology, National Ayurveda Research Institute Panchakarma, Cheruthuruthy, Thrissur - 679531, Kerala ,IN
  • G. Avinash
     Department of Pharmacology, National Ayurveda Research Institute Panchakarma, Cheruthuruthy, Thrissur - 679531, Kerala ,IN

DOI:

https://doi.org/10.18311/ti/2023/v30i4/34207

Keywords:

Acute Toxicity, AYUSH SC-3, LD50, NOAEL, OECD, 90 Days Repeated Dose Oral Toxicity

Abstract

The present study is focused on establishing the safety of the formulation through acute and 90 days of repeated oral dose toxicity as per the Organization for Economic Cooperation and Development (OECD) guidelines. During the acute toxicity test, the drug was orally administered at a limited test dose of 2000 mg/kg. Clinical signs, feed and body weight were recorded. At the end of 14 days, the animals were euthanized and subjected to a detailed post-mortem examination (necropsy). As per OECD, 408 the 90 days repeated dose oral toxicity study was carried out with three different doses of test drug i.e., 1500, 1000 and 500 mg/kg. Cage side observations, body weight and feed intake were recorded. Upon termination of the study, urine analysis, haematology and clinical biochemical examinations were performed. Finally, the rats were subjected to euthanasia, a gross necropsy was conducted and vital organs were weighed and made prone for histopathological evaluation. Cage-side observation of AYUSH-SC-3 treated animals showed no signs of toxicity, and the mortality or moribund state was observed in both of the studies. No significant change in body weight and feed intake was seen in AYUSH-SC-3 treated animals. Gross morphology and necropsy findings of the animals revealed no treatment-related. Haematological and biochemical parameters of rats treated with AYUSH-SC-3 were found to be non-significant when compared to the control group. Necropsy findings and relative organ weights did not change significantly. Further, the histopathological analysis of major organs showed no major lesions and treatment-related changes. The LD50 of AYUSH SC-3 is greater than 2000 mg/kg and NOAEL is up to 1500 mg/kg.

Downloads

Download data is not yet available.

Downloads

Published

2023-11-10

How to Cite

Gaidhani, S. N., Reddy, S. V., Ala, S., Kumar, S., Jamadagni, S., Deshmukh, P. J., Subrahmanyam, K., & Avinash, G. (2023). Safety Assessment of AYUSH SC-3 through Acute and 90 Days Repeated Dose Oral Toxicity Study. Toxicology International, 30(4), 559–572. https://doi.org/10.18311/ti/2023/v30i4/34207

Issue

Volume 30, Issue 4, October-December 2023

Section

Articles

License

Copyright (c) 2023 Sudesh N. Gaidhani, S. Viswanth Reddy, Srikanth Ala, Sanjaya Kumar, Shrirang Jamadagni, Pranita Joshi Deshmukh, K. Subrahmanyam, G. Avinash

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Crossref
Scopus
Google Scholar
Europe PMC
Received 2023-06-27
Accepted 2023-09-07
Published 2023-11-10

 

References

Patwardhan B. Historical future of Ayurveda. J Ayurveda Integr Med. 2013; 4(4):189-92. https://doi.org/10.1016/j. jaim.2016.11.004 DOI: https://doi.org/10.4103/0975-9476.123671

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. https://doi.org/10.1016/j.jep.2016.09.024 PMid:27633405 DOI: https://doi.org/10.1016/j.jep.2016.09.024

Kroes R, Walker R. Safety issues of botanicals and botanical preparations in functional foods. Toxicology. 2004; 198(1- 3):213-20. https://doi.org/10.1016/j.tox.2004.01.028 PMid: 15138044 DOI: https://doi.org/10.1016/j.tox.2004.01.028

General guidelines for safety/toxicity evaluation of Ayurvedic formulations. Volume – II; CCRAS: Ministry of AYUSH.

Botham PA. Acute systemic toxicity- Prospects for tiered testing strategies. Toxicol In Vitro. 2004; 18(2):227-30. https:// doi.org/10.1016/S0887-2333(03)00143-7 PMid:14757114 DOI: https://doi.org/10.1016/S0887-2333(03)00143-7

Vrolijk M, Deluyker H, Bast A, de Boer A. Analysis and reflection on the role of the 90-day oral toxicity study in European chemical risk assessment. Regul Toxicol Pharmacol. 2020; 117:104786. https://doi.org/10.1016/j. yrtph.2020.104786 PMid:32976858 DOI: https://doi.org/10.1016/j.yrtph.2020.104786

Taylor K, Andrew DJ. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high-quality dataset: An update. Regul Toxicol Pharmacol. 2017; 90:258-261. https:// doi.org/10.1016/j.yrtph.2017.09.018 PMid:28919391 DOI: https://doi.org/10.1016/j.yrtph.2017.09.018

OECD (Organisation for Economic Co-operation and Development). Test no. 423: Acute oral toxicity- fixed dose procedure in rodents. OECD Guidelines for the Testing of Chemicals, Section 4: Health effects. Paris: OECD Publishing; 2002.

OECD (Organisation for Economic Co-operation and Development). Test no. 408: Repeated dose 90-dayoral toxicity study in rodents. OECD Guidelines for the Testing of Chemicals, Section 4: Health effects. Paris: OECD Publishing; 2018.

Moussaoui AE, Bourhia M, Jawhari FZ, Es-Safi I, Ali SS, Bari A, Mahmood HM, Bousta D, Bari A. Withania frutescens. L Extract: Phytochemical characterization and acute and repeated dose 28-day oral toxicity studies in Mice. Biomed Res Int. 2020; 2020:1976298. https://doi.org/10.1155/2020/ 1976298 PMid:33029493 PMCid:PMC7537713 DOI: https://doi.org/10.1155/2020/1976298

Wakkumbura HP, Wickramaarachchi WMD, Arawwawala LDAM, Liyanage JA, Rajapakse RPVJ. Assessment of the quality and evaluation of the antioxidant potential of a novel Sri Lankan Ayurvedic polyherbal formulation. Evid Based Complement Alternat Med. 2020; 2020:2319315. https://doi.org/10.1155/2020/2319315 PMid:32733579 PMCid:PMC7383315 DOI: https://doi.org/10.1155/2020/2319315

Sindete M, Gbankoto A, Ganfon H, Osseni R, Yemoa A, Laleye A. Safety assessment of the ethanol of Caesalpinia bonduc (L.) Roxb. Root in wistar rats: Acute and subacute (28-day) oral toxicity studies. National Journal of Physiology, Pharmacy and Pharmacology. 2019; 9(12):1-11. https://doi.org/10.5455/njppp.2019.9.1034131102019 DOI: https://doi.org/10.5455/njppp.2019.9.1034131102019

Wang M, Qiu H, Zhang R, Long F, Mao D. Subchronic toxicity of herbal compound “Jiedu Huayu” granules in rats. BMC Complement Altern Med. 2017; 17(1):450. https:// doi.org/10.1186/s12906-017-1960-4 PMid:28877698 PMCid:PMC5585970 DOI: https://doi.org/10.1186/s12906-017-1960-4

Miaffo D, Wansi SL, Ntchapda F, Kamanyi A. Chronic oral safety study of the aqueous extract of Combretum molle twigs on biochemical, haematological and antioxidant parameters of wistar rats. BMC Complement Med Ther. 2020; 20(1):106. https://doi.org/10.1186/s12906-020- 02896-6 PMid:32248808 PMCid:PMC7133017 DOI: https://doi.org/10.1186/s12906-020-02896-6

Deyno S, Abebe A, Tola MA, Hymete A, Bazira J, Makonnen E, Alele PE. Acute and sub-acute toxicity of Echinops kebericho decoction in rats. BMC Complement Med Ther. 2020; 20(1):2. https://doi.org/10.1186/s12906-019-2794-z PMid:32020865 PMCid:PMC7076833 DOI: https://doi.org/10.1186/s12906-019-2794-z

Ugwah-Oguejiofor CJ, Okoli CO, Ugwah MO, Umaru ML, Ogbulie CS, Mshelia HE, Umar M, Njan AA. Acute and sub-acute toxicity of aqueous extract of aerial parts of Caralluma dalzielii N. E. Brown in mice and rats. Heliyon. 2019; 5(1):e01179. https://doi.org/10.1016/j.heliyon.2019. e01179 PMid:30775575 PMCid:PMC6356088 DOI: https://doi.org/10.1016/j.heliyon.2019.e01179

Lim HS, Seo YS, Ryu SM, Moon BC, Choi G, Kim JS. Twoweek repeated oral dose toxicity study of Mantidis ootheca water extract in C57BL/6 mice. Evid Based Complement Alternat Med. 2019; 2019:6180236. https://doi.org/10.1155 /2019/6180236PMid:31080484 PMCid:PMC6475539 DOI: https://doi.org/10.1155/2019/6180236

Al-Afifi NA, Alabsi AM, Bakri MM, Ramanathan A. Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats. BMC Complement Altern Med. 2018; 18(1):50. https://doi.org/10.1186/s12906-018-2110-3 PMid:29402248 PMCid:PMC5800047 DOI: https://doi.org/10.1186/s12906-018-2110-3

Teschke R, Eickhoff A. Herbal hepatotoxicity in traditional and modern medicine: Actual key issues and new encouraging steps. Front Pharmacol. 2015; 6:72. https://doi.org/10.3389/ fphar.2015.00072 PMid:25954198 PMCid:PMC4407580 DOI: https://doi.org/10.3389/fphar.2015.00072

Wang M, Guckland A, Murfitt R. et al. Relationship between magnitude of body weight effects and exposure duration in mammalian toxicology studies and implications for ecotoxicological risk assessment. Environ Sci Eur. 2019; 31:38. https://doi.org/10.1186/s12302-019-0221-1 DOI: https://doi.org/10.1186/s12302-019-0221-1

Ikechukwu GC, Egba SI, Ibeh RC, Helal EG, Ejiofor EU, Okafor PN. Assessment of sub-chronic effect of two artificial food additives on selected biochemical parameters in wistar rats. Journal of Pharmacology and Toxicology. 2017; 12:180–90. https://doi.org/10.3923/jpt.2017.180.190 DOI: https://doi.org/10.3923/jpt.2017.180.190

Kaneko JJ, Harvey JW, and Bruss ML. Kidney function. In: Clinical Biochemistry of Domestic Animals. 5th ed. Singapore: Harcourt Brace and Company Asia, Pvt. Limited. Academic Press;1999. p. 458–459.

Brar RS, Sandhu HS, and Singh A. Water, electrolyte and acid base balance. In: Veterinary Clinical Diagnosis by Laboratory Methods. 1st ed. Ludhiana, India: Kalyani Publishers; 2002. p. 115–123.

Adrogué HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med. 1981; 71(3):456-67. https://doi.org/10.1016/0002- 9343(81)90182-0 PMid:7025622 DOI: https://doi.org/10.1016/0002-9343(81)90182-0

Loha M, Mulu A, Abay SM, Ergete W, Geleta B. Acute and subacute toxicity of methanol extract of Syzygium guineense leaves on the histology of the liver and kidney and biochemical compositions of blood in rats. Evid Based Complement Alternat Med. 2019; 2019:5702159. https://doi.org/10.1155/2019/5702159 PMid:30956682 PMCid:PMC6431459 DOI: https://doi.org/10.1155/2019/5702159

Most read articles by the same author(s)