Replacement of in vivo acute oral toxicity studies by in vitro cytotoxicity methods: Opportunities, limits and regulatory status

2008 ◽  
Vol 51 (1) ◽  
pp. 108-118 ◽  
Author(s):  
Ute Ukelis ◽  
Peter-Jürgen Kramer ◽  
Klaus Olejniczak ◽  
Stefan O. Mueller
Keyword(s):  
In Vitro Cytotoxicity ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Toxicity Studies ◽  
Regulatory Status

scholarly journals In Vivo and In Vitro Toxicity Profiles of Hexane Extract of Alpinia malaccensis Rhizome in Rat and Cell Line Models

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
T. Somarathna ◽  
M. G. Thammitiyagodage ◽  
K. K. D. S. Ranaweera ◽  
G. A. S. Premakumara ◽  
M. A. Akbarsha ◽  
...  
Keyword(s):  
Body Weight ◽  
Biochemical Parameters ◽  
Lethal Dose ◽  
In Vitro Cytotoxicity ◽  
Hexane Extract ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Hematological And Biochemical Parameters

The objective of the study was to evaluate the potential toxicity of crude n-hexane extract of Alpinia malaccensis rhizome. The in vivo acute oral toxicity was evaluated by administering a single oral dose of the extract at 0, 300, or 2000 mg/kg body weight to female Wistar rats according to modified OECD Test Guideline 423. For the in vitro cytotoxicity study, A549, HepG2, 3T3, and COS-7 cell lines were exposed to different doses of A. malaccensis extract and cell viability was assessed adopting MTT assay followed by AO/EB staining, Hoechst staining, and comet assay with a view to compare the cellular and molecular mechanisms underlying the toxicity, if any. It was found that administration of 2000 mg/kg bw dose in in vivo oral acute toxicity study did not produce significant toxicity or mortality. No significant ( p < 0.05 ) differences were observed for body weight and hematological and biochemical parameters compared to control after 14 days of treatment. No changes in behavior, body weight, hematological and biochemical parameters, and aspects of histopathology were observed when compared to the control. Thus, the possible oral lethal dose for A. malaccensis extract is above 2000 mg/kg body weight. The in vitro cytotoxicity analysis showed nontoxicity concentrations of the extract to be 2, 1.4, 30, and 1.4 µg/mL for A549, HepG2, 3T3, and COS-7 cells, respectively, where no apoptotic/necrotic cell death and DNA damage were observed. In conclusion, the extract of rhizome of A. malaccensis did not produce apparent cytotoxicity or acute oral toxicity, confirming the scope to use A. malaccensis as a safe food preservative and a natural therapeutic product after further subacute and chronic toxicity studies.

Safety Evaluation of a Proprietary Food-Grade, Dried Fermentate Preparation of Saccharomyces cerevisiae

2012 ◽  
Vol 31 (1) ◽  
pp. 34-45 ◽  
Author(s):  
Alexander G. Schauss ◽  
R. Glavits ◽  
John Endres ◽  
Gitte S. Jensen ◽  
Amy Clewell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Clinical Symptoms ◽  
Safety Evaluation ◽  
In Vivo Studies ◽  
Oral Toxicity ◽  
Toxicity Studies ◽  
Adverse Effect Level ◽  
Effect Level

A safety evaluation was performed for EpiCor, a product produced by a proprietary fermentation process using Saccharomyces cerevisiae. Studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome P450 ([CYP] CYP1A2 and CYP3A4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. No evidence of genotoxicity or mitogenicity was seen in any of the in vitro or in vivo studies. The CYP assessment showed no interactions or inductions. No toxic clinical symptoms or histopathological lesions were observed in the acute, subchronic, or chronic oral toxicity studies in the rat. Results of the studies performed indicate that EpiCor does not possess genotoxic activity and has a low order of toxicity that is well tolerated when administered orally. The no observable adverse effect level (NOAEL) was 1500 mg/kg body weight (bw)/d for the 90-day study and 800 mg/kg bw/d for the 1 year study, for the highest doses tested.

A comprehensive biological insight of trinuclear copper(ii)–tin(iv) chemotherapeutic anticancer drug entity: in vitro cytotoxicity and in vivo systemic toxicity studies

Metallomics ◽  
2014 ◽  
Vol 6 (8) ◽  
pp. 1469 ◽  
Author(s):  
Yusra Zaidi ◽  
Farukh Arjmand ◽  
Nida Zaidi ◽  
Jawed Ahmad Usmani ◽  
Haseeb Zubair ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
In Vitro Cytotoxicity ◽  
Systemic Toxicity ◽  
Toxicity Studies ◽  
Biological Insight

scholarly journals Anti-malarial activity and toxicity of Aspidosperma nitidum Benth: a plant used in traditional medicine in the Brazilian Amazon

2020 ◽  
Vol 9 (10) ◽  
pp. e5059108817
Author(s):  
Dayse Lucia do Nascimento Brandão ◽  
Michel Tavares Martins ◽  
Adreanne Oliveira Silva ◽  
Amanda Dias Almeida ◽  
Renata Cristina de Paula ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Neutral Fraction ◽  
Antiplasmodial Activity ◽  
Major Constituent ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Alkaloid Fraction ◽  
Low Cytotoxicity

The objective of this work was to evaluate the antiplasmodial activity and toxicity of the extract and fractions obtained from the bark of Aspidosperma nitidum. The ethanol extract obtained from the powdered bark of plants was acid-base partitioned and phytochemically analyzed. The antiplasmodial activity, in vivo antimalarial activity and in vitro cytotoxicity were acessed. The selectivity index (SI) was calculated. The acute oral toxicity and pathological effects, of the ethanol extract was evaluated in mice. The major constituent of the ethanol extract was suggestive of a β-carboline chromophore. The alkaloid and neutral fractions contained compounds with an aspidospermine core as the major constituent. The ethanol extract (IC50 = 3.60 µg/mL), neutral fraction (IC50 = 3.34 µg/mL) and alkaloid fraction (IC50= 2.32 µg/mL) showed high activity against P. falciparum (W2 strain). The ethanol extract and the alkaloid fraction reduced 80% of the parasitemia of P. berghei (ANKA)-infected mice (dose of 500 mg/kg) in the 5th day, which was not sustainable at the 8th day. A similar result was obtained for chloroquine. The ethanol extract (CC50 = 410.65 µg/mL; SI = 114.07), neutral fraction (CC50 = 452.53 µg/mL; SI = 135.49), and alkaloid fraction (CC50 =346.73 µg/mL; SI 149.45) demonstrated low cytotoxicity and high SI. The ethanol extract (5000 mg/kg; gavage) presented low acute oral toxicity, with no clinical or anatomopathological modifications being observed (in comparison to the control group). In vitro studies with a chloroquine-resistant clone of P. falciparum confirmed the antiplasmodial activity of the A. nitidum ethanol extract, and its fractions had low cytotoxicity for HepG2 cells. In vivo studies with P. berghei–infected mice and acute toxicity studies corroborated these results.

scholarly journals Acute, subacute oral toxicity and Ames test of Py-mulin: an antibacterial drug candidate

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yuan Fan ◽  
Yunxing Fu ◽  
Yuhang Zhou ◽  
Yu Liu ◽  
Baocheng Hao ◽  
...  
Keyword(s):  
Ames Test ◽  
Clinical Chemistry ◽  
Toxicity Study ◽  
Female Rats ◽  
Drug Candidate ◽  
Antibacterial Drug ◽  
Acute Oral Toxicity ◽  
Oral Toxicity

Abstract Background Py-mulin is a new pleuromutilin derivative with potent antibacterial activities in vitro and in vivo, suggesting this compound may lead to a promising antibacterial drug after further development. The present study is aimed to evaluate the acute and subacute oral toxicity, and the genotoxicity with the standard Ames test according to standard protocols. Methods Acute oral toxicity of Py-mulin was determined using Kunming mice. The 28-day repeated dose oral toxicity study in SD rats was performed according to OECD guideline No. 407. The bacterial reverse mutation (Ames test) was carried out using four Salmonella typhimurium (S. typhimurium) strains TA97, TA98, TA100 and TA1535 with and without S9 metabolic activation. Results The LD50 values in acute oral toxicity were 2973 mg/kg (female mice) and 3891 mg/kg (male mice) calculated by the Bliss method. In subacute toxicity study, 50 mg/kg Py-mulin did not induce any abnormality in body weight, food consumption, clinical sign, hematology, clinical chemistry, organ weight, and histopathology in all of the treatment groups. However, high doses of Py-mulin (100 and 300 mg/kg) displayed slightly hepatotoxicity to female rats. Furthermore, Py-mulin did not significantly increase the number of revertant colonies of four standard S. typhimurium strains with the doses of 0.16–1000 μg/plate in the Ames study. Conclusions Based on our findings, our study provides some information for the safety profile of Py-mulin.

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