Cyst-Based Toxicity Tests. IV. The Potential of Ecotoxicological Tests for the Prediction of Acute Toxicity in Man as Evaluated on the First Ten Chemicals of the MEIC Programme

1992 ◽  
Vol 20 (3) ◽  
pp. 396-405 ◽  
Author(s):  
Mabel C. Calleja ◽  
Guido Persoone
Keyword(s):  
Acute Toxicity ◽  
Brachionus Plicatilis ◽  
Artemia Salina ◽  
In Vitro Cytotoxicity ◽  
Aquatic Invertebrate ◽  
Toxicity Tests ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Aquatic Test Systems

In the framework of the multicentre evaluation of in vitro cytotoxicity (MEIC) programme, the first ten chemicals of the prescribed list were tested for acute toxicity in four standardised cyst-based aquatic invertebrate tests, consisting of two rotifer species (the estuarine Brachionus plicatilis and the freshwater Brachionus calyciflorus) and two crustacean species (the halophilic anostracan Artemia salina and the freshwater anostracan Streptocephalus proboscideus). Mortality was the test criterion and toxic effects, expressed as 24-hour LC50 values, were correlated with rodent and human acute oral toxicity data. Generally, a good correlation was obtained between any of the invertebrate tests and the rodent data. Likewise, the predictive screening potential of the aquatic invertebrate tests for acute oral toxicity in man was slightly better than the rat test for eight (excluding diazepam and digoxin) and nine (including diazepam, excluding digoxin) of the ten substances. The aquatic test systems, however, appear to be more suitable for compounds soluble in water.

Toxicity Evaluation, HET-CAM Irritation, and Anti-Irritant Potential of Rice Bran Wax Policosanol Nanoemulsion

2017 ◽  
Vol 49 ◽  
pp. 44-55 ◽  
Author(s):  
Aminu Ishaka ◽  
Maznah Ismail ◽  
Mustapha Umar Imam ◽  
Rozi Mahmud ◽  
Ismaila Muhammad Sani ◽  
...  
Keyword(s):  
Body Weight ◽  
Rice Bran ◽  
Biological Effects ◽  
Toxicity Tests ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Rice Bran Wax ◽  
Toxicological Studies ◽  
Limit Test

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects. However, it has a bioavailability of less than 10%. One of the ways of improving bioavailability is by nanoemulsion formulation. We developed rice bran wax policosanol nanoemulsion (npol) using high-pressure homogenization. Even though earlier toxicological studies did not show policosanol-related toxicity, it is an essential part of the development of the therapeutic formulation to evaluate its toxicity status. In this study, in vitro, in vivo toxicity, and irritation and anti-irritation potential of the npol were evaluated. 3T3-L1 cells and Sprague Dawley rats were treated with npol in the in vitro and acute oral toxicity tests; while the Hen’s Egg Test Chorio-Allantoic membrane (HET-CAM) was used to test for its irritation and anti-irritation potential. npol at 2mg/mL showed lower toxicity to 3T3-L1 cells by MTT assay compared to the same concentration of policosanol after 24 (60 and 50% viabilities), 48 (62 and 58% viabilities), and 72 (110 and 89% viabilities) hours, respectively. npol was non-irritant and has slightly anti-irritant potential based on the HET-CAM test. There was also no significant toxicity to a limit test dose of 40 ml/Kg body weight of npol (containing 2000 mg/Kg body weight of policosanol) in acute oral toxicity test on Sprague-Dawly rats. The results suggest that policosanol nanoemulsion is a safe formulation devoid of toxicity and irritation potential.

scholarly journals ACUTE TOXICITY TESTING OF NEWLY DISCOVERED POTENTIAL ANTIHEPATITIS B VIRUS AGENTS OF PLANT ORIGIN

2017 ◽  
Vol 10 (11) ◽  
pp. 210 ◽  
Author(s):  
Subaiea Gm ◽  
Aljofan M ◽  
Devadasu Vr ◽  
Alshammari Tm
Keyword(s):  
Acute Toxicity ◽  
Antiviral Activity ◽  
Toxicity Testing ◽  
Acute Oral Toxicity ◽  
Isoquinoline Alkaloids ◽  
Oral Toxicity ◽  
B Virus ◽  
Low Cytotoxicity

Objective: Our previous studies indicate that alkaloids could be developed as potential antihepatitis B agents. In the present study, we investigated the in vitro antihepatitis B virus (HBV) activity and in vivo acute oral toxicity of three isoquinoline alkaloids [-(-) Canadine, Corydadine, and Berberine] obtained from Fumaria and Corydalis species. The compounds were selected based on their therapeutic indexes calculated previously in vitro.Methods: The antiviral activity and cytotoxicity of selected isoquinoline alkaloids were evaluated in vitro in HepG2 cells. In vivo, acute oral toxicity was performed in female mice following the Organization for Economic Cooperation and Development test guideline-423 (acute toxicity class method).Results: The selected agents have shown high antiviral activity against HBV and low cytotoxicity in vitro. The results obtained from an acute oral toxicity study revealed that the LD50 of all the test compounds was >2000 mg/kg when administered orally to mice. All the tested compounds fall under the category 5 (unclassified) according to the Globally Harmonized System, with a LD50 value >2000 mg/kg when orally administered to mice.Conclusion: The results of the study revealed that OR-13 and MNAD can be studied further and can be developed as antihepatitis B drugs.

Evaluation of the BTS Approach to the Testing of Substances and Preparations for their Acute Toxicity

1987 ◽  
Vol 6 (4) ◽  
pp. 279-291 ◽  
Author(s):  
M.J. van den Heuvel ◽  
A.D. Dayan ◽  
R.O. Shillaker
Keyword(s):  
Risk Assessment ◽  
Acute Toxicity ◽  
Animal Welfare ◽  
Toxicity Testing ◽  
Toxic Effects ◽  
Toxicity Tests ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
New Approach ◽  
Human Risk

This study has shown that the new approach to acute oral toxicity testing proposed by the British Toxicology Society 1 provides the information on the toxic effects of materials necessary for human risk assessment, 2 can be used to rank materials for regulatory purposes on the basis of their acute toxicity, 3 provides advantages for animal welfare by requiring the use of fewer animals than conventional acute oral toxicity tests and by subjecting those animals used to less chance of experiencing pain or distress.

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.

The Predictive Potential of a Battery of Ecotoxicological Tests for Human Acute Toxicity, as Evaluated with the First 50 MEIC Chemicals

1993 ◽  
Vol 21 (3) ◽  
pp. 330-349 ◽  
Author(s):  
Mabel C. Calleja ◽  
Guido Persoone ◽  
Paul Geladi
Keyword(s):  
Least Squares Method ◽  
Artemia Salina ◽  
In Vitro Cytotoxicity ◽  
Photobacterium Phosphoreum ◽  
Toxicity Tests ◽  
Ecotoxicological Tests ◽  
Partial Least Squares Method ◽  
Lethal Doses ◽  
Better Than

The acute toxicities of the first 50 chemicals (dextropropoxyphene hydrochloride excluded) of the multicentre evaluation of in vitro cytotoxicity (MEIC) programme were determined on four aquatic invertebrates and a bacterial strain (Photobacterium phosphoreum for the Microtox™ test) commonly used in ecotoxicology testing. Three of the aquatic invertebrate tests consisted of cyst-based toxicity tests (Artoxkit M with Artemia salina, Streptoxkit F with Streptocephalus proboscideus, and Rotoxkit F with Brachionus calyciflorus), and the Daphnia magna test. Results of simple linear regression analyses indicated that the rodent tests (rat and/or mouse) were better than the ecotoxicological tests for predicting acute oral lethal doses in man. However, it appears that the batteries of ecotoxicological tests resulting from the partial least squares method appear to be better than the rodent tests for predicting human oral lethal doses.

Acute toxicity of an insecticidal little containing ivermectin and fipronil for white mice

2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  
Keyword(s):  
Acute Toxicity ◽  
Lethal Dose ◽  
Live Weight ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Russian Research Institute ◽  
Veterinary Entomology ◽  
Russian Research

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.

scholarly journals In vitro Assessment of Antiplasmodial Activity and Acute Oral Toxicity of Dissotis rotundifolia Extracts and Fractions on Plasmodium falciparum Strains

2020 ◽  
pp. 8-19
Author(s):  
Rock Djehoue ◽  
Rafiou Adamou ◽  
Abdou Madjid O. Amoussa ◽  
Adande A. Medjigbodo ◽  
Anatole Laleye ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Acute Toxicity ◽  
Ethanolic Extract ◽  
Antiplasmodial Activity ◽  
Oral Toxicity ◽  
Aqueous Fraction ◽  
Vector Borne Diseases ◽  
Natural Substances ◽  
Study Laboratory

Aim: Dissotis rotundifolia were selected after an ethnopharmacological survey conducted on plants used traditionally for malaria treatment in South Benin, with the aim of discovering new natural active extracts against malaria parasites. Place and Duration of Study: Laboratory of Biochemistry and Bioactive Natural Substances, University of Abomey-Calavi (Benin)/ Laboratory of Infectious Vector Borne Diseases, Regional Institute of Public Health (Benin)/ Laboratoire d’Histologie, de Cytogénétique et d’Embryologie, Faculté des Sciences de la Santé (Benin). The study was conduct from October 2018 to June 2019 in Benin. Methodology: The antiplasmodial activity of the plant extracts was evaluated using the parasite lactate dehydrogenase (pLDH) immunodetection assay. The extract with the best antiplasmodial activity were used on Wistar rats for acute toxicity. Results: Ethanolic extract of Dissotis rotundifolia showed promising activity (Isolate: IC50 = 22.58 ± 1.12 µg/mL; 3D7: IC50 = 6.81 ± 0.85 µg/mL) on Plasmodium falciparum compared to the aqueous extract (Isolate: IC50 > 100 µg/mL; 3D7: IC50> 100 µg/mL). The aqueous fraction of D. rotundifolia exhibit highly potent activity against P. falciparum strain (Isolate: IC50 > 100 µg/mL μg/mL; 3D7: IC50 = 4.05 ± 0.72 μg/mL). Haemolytic effect of actives extracts and fractions is less than 5%. Ethanolic extract of D. rotundifolia revealed no obvious acute toxicity in rat up to the highest dose administered (2000 mg/kg). Conclusion: This study justifies traditional uses of D. rotundifolia against malaria. A bioguided fractionation of these extracts would identify molecules responsible for their antiplasmodial activity. Moreover, these results could lead to the design of improved traditional medicines in the basis of this plant.

scholarly journals ACUTE ORAL TOXICITY ASSESSMENT OF THE ETHANOL EXTRACT OF HOLOTHURIA ATRA IN MICE

2019 ◽  
pp. 150-153
Author(s):  
PANDU SALIM HANAFI ◽  
AJI SUTRISNO ◽  
TUTIK MURNIASIH ◽  
HARIJONO ◽  
MASTERIA YUNOVILSA PUTRA ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Toxicity Test ◽  
Ethanol Extract ◽  
Polar Compounds ◽  
Toxicity Assessment ◽  
Acute Oral Toxicity ◽  
Test Results ◽  
Oral Toxicity ◽  
Ethanol Extracts ◽  
Holothuria Atra

Objective: This study aimed to evaluate the toxicological potential of the ethanol extract of Holothuria atra through the acute oral toxicity – acute toxic class method. Methods: The sample was immersed in ethanol for 72 h at room temperature and repeated 3 times. The extracts were evaporated using a vacuum rotary evaporator. The identification of compounds in the ethanol extract of H. atra was carried out using liquid chromatography–mass spectrometry (LCMS) analysis. The acute toxicity test was examined the effects of treating male mice with the ethanol extract of H. atra at 300 and 2000 mg/kg by oral administration for 14 days. On the past day of the toxicity test, liver of all experimental animals was taken for histopathological testing. Results: LCMS analysis showed that the ethanol extract of H. atra is contained polar compounds (chlorogenic acid, coumaric acid, a glycosaminoglycan, and holothurin) and non-polar compounds (fatty acids). Acute toxicity study was performed at a dose of 300 and 2000 mg/kg for 14 consecutive days. No deaths or behavioral changes were observed during the administration of both doses. Histopathological test results on the liver showed a few changes at doses of 2000 mg/kg. Conclusions: The LD50 is equal to 5000 mg/kg and the ethanol extracts of H. atra can be classified as practically nontoxic. However, further studies are required to proceed to clinical studies in humans.

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