2014b;4:17–25. Sections of the heart taken from both male and female rats appeared normal in control treated as well as extract treated rats, however in male rats mild haemorrhage was observed. In our study a single administration of extract with increasing doses did not produce any mortality or any serious abnormities at all doses in acute toxicity, however, the mild sedative effect was noticed in both male and female rats at a single dose of 2000 mg/kg, b.wt. 2014;47:55. In female rats, a decrease in glucose, urea, albumin, SGPT, SGOT, and ALP was observed which were mainly significant when compared to control. Traditional use and safety of herbal medicines. 2007;112:138–44. The body weights were also recorded prior to testing and terminally (after fasting) prior to necropsy. In the sub-acute study, no severe treatment-related toxicity was observed during the study after the rats were administered with ARELE up to a dose of 500 mg/kg b.wt., for a period of 30 days. Decrease in haemoglobin and monocytes content were observed except for ARELE at a low dose which showed an increase in haemoglobin when compared with the control. 2018;92:315–23. Signalez des exemples à modifier ou à retirer. 2017;7:207–16. The relative weight of liver, kidney, pancreas, and heart was almost similar to that of control and decrease in relative weight was observed for stomach and ovary which was significant (P < 0.01) and non-significant respectively in a dose dependant manner. © 2020 BioMed Central Ltd unless otherwise stated. There were no clinical signs of toxicity observed for the normal control group. Photomicrographs of histological findings of different organs from male rats treated with normal control vehicle and ARELE at high dose (500 mg/kg, b.wt.) Some of the traditionally used medicinal plants such as Larrea tridentata (DC. Acute toxicity is considered an initial study which provides us the basis for classification and labelling. Rats of both sexes were used for the study. Parasuraman S. Toxicological screening. Ghosh, D., Mondal, S. & Ramakrishna, K. Acute and sub-acute (30-day) toxicity studies of Aegialitis rotundifolia Roxb., leaves extract in Wistar rats: safety assessment of a rare mangrove traditionally utilized as pain antidote. 2002;10:421–52. Acute systemic toxicity assaying is the most commonly performed, and includes a single exposure with a 72-hour observation period. Triglycerides and cholesterol levels (Total cholesterol, HDL cholesterol, LDL cholesterol, and VLDL cholesterol) increased mostly significantly in a non-dose dependant manner when compared with the control. (n = 6). Bei Beaglehunden scheint kein wesentlicher Unterschied hinsichtlich der akuten Toxizität zu bestehen. All animals were fasted overnight prior to necropsy. In Orissa it is locally known as Banrua [7]. The rest of the parameters showed minor fluctuations mostly non-significantly when compared with the control. 3 and 4. Wolf G, Ziyadeh FN. The number of obstructions recorded for extracts was compared with the control group. Clinical biochemistry analysis was conducted to investigate any possible influence of the extract on hepatic and renal functions of rats. This Biocompatibility Subacute/Subchronic Toxicity testing complies with ISO 10993-11. Sumanta Mondal. Die subakute Toxizität wird im Tierversuch bestimmt. a Male rats. Graca C, Freitas CS, Baggio CH, Dalsenter PR, Marques MCA. In male rats’ mild haemorrhage was found in kidney and heart, whereas mild lymphocytic infiltrations and mild hyperplastic changes were found on lungs and stomach respectively. Zhang J, Onakpoya IJ, Posadzki P, Eddouks M. The safety of herbal medicine: from prejudice to evidence. Acute oral toxicity and neurobehavioural toxicological effects of hydroethanolic extract of Boophone disticha in rats. 2014;151:1155–64. 2011;39:36–45. In subacute tests, the photoisomer has been shown to be more toxic than HEOD to mice. Systemic toxicity assays evaluate a test article’s potential to induce a systemic response after exposure. Cookies policy. Acute, subacute, subchronic and chronic toxicity, Dose routes: IV, IP, IM, subcutaneous, dermal, and oral, 14-Day IV and /or IP Subacute Toxicity Study, 5,040 cm² (IV), 450 (IP) <0.5 mm thick, 2,520 (IV), 225 (IP) cm² ≥0.5 mm thick, or 168 grams (IV), 30 grams (IP), 28-Day IV and /or IP Subchronic Toxicity Study, 10,080 cm² (IV), 900 (IP) <0.5 mm thick, 5,090 cm² (IV), 450 (IP) cm² ≥0.5 mm thick, or 336 grams (IV), 60 grams (IP). Effects of ARELE on behavioural endpoints of the FOB on initial week (Day 0). In the Biocompatibility Subacute/Subchronic Toxicity test, mice or rats will be administered, intravenously or intraperitoneally, a dose of 0.9% normal saline or cotton seed extract of the test article/vehicle control 14 times over a 14-day test period. Acute and sub-acute toxicity studies on the effect of Senna alata in Swiss Albino mice S. Roy 1, B. Ukil and L.M. 423, Adopted 22nd March 1996, and Revised Method Adopted 17th December 2001, OECD, Paris. 1998;2:133–48. Manage cookies/Do not sell my data we use in the preference centre. ): Die subakute Toxizität von Stoffen kann gemäß der Stoffrichtlinie RL 67/548/EWG, Anhang VI, Kapitel 3 ein Kriterium zur Einstufung des Stoffes entweder als giftig oder als gesundheitsschädlich sein. The limit test dose for the study was 2000 mg/kg, b.wt. $$ \mathrm{Percentage}\ \mathrm{yield}=\frac{\mathrm{weight}\ \mathrm{of}\ \mathrm{dry}\ \mathrm{crude}\ \mathrm{extract}\ \mathrm{obtained}\ \left(\mathrm{g}\right)}{\mathrm{weight}\ \mathrm{of}\ \mathrm{plant}\ \mathrm{material}\ \mathrm{before}\ \mathrm{extract}\mathrm{ion}\left(\mathrm{g}\right)}\times 100 $$, $$ \mathrm{ROW}=\left[\frac{\mathrm{Absolute}\ \mathrm{organ}\ \mathrm{weight}\left(\mathrm{g}\right)}{\mathrm{Body}\ \mathrm{weight}\ \mathrm{of}\ \mathrm{rat}\ \mathrm{on}\ \mathrm{sacrifice}\ \mathrm{day}\left(\mathrm{g}\right)}\right]\times 100 $$, http://creativecommons.org/licenses/by/4.0/, https://doi.org/10.1186/s40816-019-0106-2. Our study demonstrated that in male rats, after administration of extract at different doses all organs increased mostly significantly except stomach which showed a decrease in weight, whereas in female rats only stomach and ovary showed decrease in their weight. The result of the FOB has been given in the Additional file 1: Tables S4 and S5. In the evaluation of acute toxicity, oral administration of ARELE at a dose up to 2000 mg/kg b.wt., did not produce any major toxicological effects except for mild short-term sedation after administration of the limit test dose of 2000 mg/kg b.wt. All the statistical significance calculated was compared with the control. Article 2007;72:215–9. 412: Subacute Inhalation Toxicity: 28-Day Study OECD Guidelines for the Testing of Chemicals, Section 4 Health Effects The OECD Guidelines for the Testing of Chemicals is a collection of about 150 of the most relevant internationally agreed testing methods used by government, industry and independent laboratories to identify and characterise potential hazards of chemicals. d Relative organ weight of female rats. All authors revised and approved the final manuscript. According to current literature A. rotundifolia has not been investigated for their toxicological property which is used traditionally as a pain reliever by local healers of mangroves. Diese Prüfungen sollten dazu beitragen, die Zielorgane der toxischen Wirkungen sowie die toxischen und nichttoxischen Dosen zu ermitteln. In sub-acute toxicity, the extract at the doses of 125, 250 and 500 mg/kg, b.wt., was administered orally for 30 days. Mattsson JL, Spencer PJ, Albee RR. This tool is a non-invasive procedure developed to detect gross functional deficits in young adult rats after they have been exposed to drugs or chemicals. Multiple sections of the male liver showed normal hepatocytes along with normal portal triads, sinusoidal spaces and central venous system in extract treated group. Aus der subakuten dermalen und der subakuten inhalativen Toxizität kann der NOAEL-Wert hergeleitet werden. In both male and female rats, no abnormalities in home cage observations like posture, presence or absence of tremors and convulsions, spontaneous vocalization and biting were noted for both the control and the extract treated group at different doses. FOB was performed according to standard procedures [22, 23] with few minor modifications. However, there are no scientific reports of its toxicological properties which would guarantee the safety of its folkloric usage as a potent pain reliever. According to the current literature the toxicological effects of A. rotundifolia has not been studied at all. However, further study is required to investigate and confirm its safety and effectiveness in humans. The test group rats received ARELE at the doses of 1000, 1500, and 2000 mg/kg, b.wt., once orally as test sample, which was prepared by suspending ARELE in tween 20 solution (1%, v/v) and mixed thoroughly. Haematological profile of the blood samples kept in sterile tubes containing anticoagulant was analysed using automatic haematological analyser (Sysmex XS-1000i). These findings were not considered toxicologically important as the changes were minimal when compared to the normal control group. The serum obtained was stored at − 20 °C for later use. Mohamed EAH, Lim CP, Ebrika OS, Asmawi MZ, Sadikun A, Yam MF. Toxicol Pathol. Urine from all animals was collected overnight using metabolic cages (Nalgene, USA) and parameters such as pH, specific gravity, leukocytes, nitrites, proteins, blood, ketones, glucose, urobilinogen and bilirubin were examined. Balogun SO, Da Silva IF, Colodel EM, De Oliveira RG, Ascêncio SD, De Oliveira Martins DT. The dosing volume was 10 mL/kg and was orally administered once daily through oral gavage. 2013;2013:804086. c Relative organ weight of male rats. All the other parameters showed non-significant and non-dose dependant changes when compared with the control. On the final week of the treatment period after the administration of ARELE at different doses to both male and female rats, the actophotometer reading (no. „Achtung“, den H-Sätzen H 372 bzw. Die Ergebnisse aus der subakuten Toxizität werden unter Angabe des Expositionsweges, der Tierspezies und der Prüfmethode angegeben. Department of Chemistry, GITAM Institute of Science, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, India, GITAM Institute of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, 530045, India, You can also search for this author in If you have additional questions about the Subacute/Subchronic Toxicity test, or would like to consult with the experts at Nelson Labs, just send us a request or call us at +1 (801) 290-7500. 2015;5:2–38. The vital organs were removed and placed on absorbent papers for few minutes and weighed to give their absolute organ weight (g). Pas de publicités. The cage beddings and water bottles were cleaned on daily basis. J Ethnopharmacol. In our study, the urine analysis revealed minor increase in bilirubin, glucose, ketone bodies, and WBC content in high dose group for male rats, whereas minor increase in ketone bodies, Protein, and WBC content was observed for female rats. The control group which was administered with normal vehicle (tween 20 solution (1%, v/v)) did not produce any toxic effects or mortality within the study period. Mangrove plants are a rich source of alkaloids, flavonoids, triterpenes, steroids, saponins, and tannins. Google Scholar. However, there was a slight increase in the levels of triglyceride and cholesterol levels mostly non-significantly for both male and female rats which might indicate that the extract might induce obesity. volume 5, Article number: 13 (2019) Enregistez-vous pour voir plus d'exemples. The results showed that in male rats, the body weight in the test extract treated groups increased non-significantly (P > 0.05) except in day 20 where the increase in body weight was significant (P < 0.05) for ARELE (500 mg/kg, b.wt.) Es ist vorteilhaft, vorher Angaben zur Partikelgrößenverteilung, zum Dampfdruck, Schmelzpunkt, Siedepunkt, Flammpunkt und zur Explosivität (falls zutreffend) der Substanz zu haben. *P < 0.05 compared to control group. J Am Coll Toxicol. Int J Pharm Sci Drug Res. Regul Toxicol Pharmacol. None of the rats (both male and female) after administration of ARELE at the doses of 125, 250 and 500 mg/kg, b.wt., showed any obvious morbidity or clinical symptoms of toxicity such as changes in the skin and fur, eyes, respiratory rate, autonomic (salivation, perspiration and piloerection), and stereotype activities throughout the experimental period of 30 days. Les traductions vulgaires ou familières sont généralement marquées de rouge ou d’orange. The preliminary phytochemical test of ARELE was conducted and the result revealed the presence of alkaloids, carbohydrates, tannins and phenolic compounds, steroids and sterols, triterpenoids, saponins and flavonoids. Ukwuani AN, Abubakar MG, Hassan SW, Agaie BM. Histopathological analysis of the organ samples of liver, kidney, pancreas, heart, lungs, and stomach from both male and female rats whereas testis and ovary from male and female rats respectively were performed on the final day of the treatment period and the results are tabulated in Figs. Traditional and medicinal uses of mangroves. In female rats, haemoglobin, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), neutrophils and eosinophils increased mostly in a non-significant manner, whereas WBC content decreased non-significantly along with platelets (PLT) and lymphocytes count which showed significant (P < 0.01) decrease in a dose dependant manner when compared with the control. S Afr J Bot. Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Sub-acute toxicity profile of a modified resveratrol supplement Food Chem Toxicol. The route of exposure should be chosen based on clinical relevance. The counts were recorded when the beam of light falling on the photocell of actophotometer is cut off by rats. Plant products can also produce toxic effects and thus to ensure its safety, systematic studies regarding its toxic effects needs to be evaluated as a result providing scientific information for selecting safe doses for animals including humans [27]. for a period of 30 days (H&E staining, 40 × magnification). In the Biocompatibility Subacute/Subchronic Toxicity test, mice or rats will be administered, intravenously or intraperitoneally, a dose of 0.9% normal saline or cotton seed extract of the test article/vehicle control 14 times over a 14-day test period. Evaluation of haematological parameters would be helpful in determining the toxic effects of the extract on animal’s blood and thus can be used to explain blood relevant function of extracts [33].