A New Heterocyclic 1H-perimidine synthesized 2-(2,3-dihydro-1H-périmidin-2yl-)-6-methoxyphenol: Evaluation of Acute Toxicity in Wistar Rat

Background and Aim: The 1H-perimidne, as novel source carbene ligand, is well known for its anti-fungal, anti-microbial or anti-tumor activities. Here, we aimed to study the acute toxicity in Wistar rat of 2-(2,3-dihydro-1H-perimidin-2-yl)-6-methoxyphenol, a new heterocyclic 1H- perimidine synthetized in our laboratory. Materials and Methods: Five groups of males Wistar rats were intraperitoneally injected with 7 mg/kg, 40 mg/kg, 90 mg/kg, 130 mg/kg and 150 mg/kg dissolved in dimethyl sulfoxide (DMSO), and followed during 14 days. We noted any clinical signs of acute toxicity as body weight loss, salivation, tremor, convulsion among others, as well as food consumption and water intake level. Results: The DL50 of the new 2-(2,3-dihydro-1H-perimidin-2-yl)-6-methoxyphenol was estimated to 65 mg/kg. The No Observed Adverse Effect Level (NOAEL) dose was 7 mg/kg because it did not caused mortality, clinical signs of acute toxicity, and not affected feed and water intake behavior. However, significant abnormalities as inflammation and necrosis were observed at doses-effects dependent in liver, when compared to NOAEL dose and vehicle. Conclusion: The new heterocyclic 2-(2,3-dihydro-1H-perimidin-2-yl)-6-methoxyphenol is considered as high toxicity grade product. From NOAEL dose, subsequent biological, toxicological, pharmacological and neurobehavioral studies are needed before using for clinical trials.

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Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies

Human & Experimental Toxicology ◽

10.1177/0960327109346789 ◽

2009 ◽

Vol 28 (10) ◽

pp. 619-630 ◽

Cited By ~ 17

Author(s):

T. Kobayashi ◽

N. Yasutake ◽

K. Uchida ◽

W. Ohyama ◽

K. Kaneko ◽

...

Keyword(s):

Oral Dose ◽

Kluyveromyces Lactis ◽

Clinical Signs ◽

Chinese Hamster ◽

Metabolic Activation ◽

Blood Chemistry ◽

Control Group ◽

Sprague Dawley ◽

Adverse Effect Level ◽

Effect Level

A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.

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Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

International Journal of Toxicology ◽

10.1177/1091581812437974 ◽

2012 ◽

Vol 31 (3) ◽

pp. 250-256 ◽

Cited By ~ 4

Author(s):

Darol E. Dodd ◽

Linda J. Pluta ◽

Mark A. Sochaski ◽

Kathleen A. Funk ◽

Russell S. Thomas

Keyword(s):

Adverse Effect ◽

Body Weight ◽

Exposure Time ◽

Clinical Signs ◽

Liver Weight ◽

Sprague Dawley ◽

Significant Incidence ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

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ACUTE AND SUB CHRONIC TOXICITY STUDIES OF PURIFIED WITHANIA SOMNIFERA EXTRACT IN RATS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i12.29493 ◽

2018 ◽

Vol 10 (12) ◽

pp. 41 ◽

Cited By ~ 2

Author(s):

Benny Antony ◽

Merina Benny ◽

Binu T. Kuruvilla ◽

Nishant Kumar Gupta ◽

Anu Sebastian ◽

...

Keyword(s):

Acute Toxicity ◽

Dose Level ◽

Chronic Toxicity ◽

Withania Somnifera ◽

Clinical Signs ◽

Repeated Administration ◽

Female Rats ◽

Toxic Effects ◽

Toxicity Studies ◽

Adverse Effect Level

Objective: The objective of the present study was to evaluate the acute and sub-chronic (90 d; repeated dose) toxicity of Withania somnifera (ashwagandha) extract in rats.Methods: The acute toxicity was evaluated as per OECD (Organisation for Economic Co-operation and Development) guidelines 423. Purified ashwagandha extract (PAE) was fed at 2000 mg/kg body weight (bw) to overnight fasted female rats. The animals were observed daily for clinical signs of abnormality/mortality. After 14 d, animals were sacrificed and gross pathological changes were recorded. Sub-chronic toxicity of PAE was studied by feeding the extract at 100, 500 and 1000 mg/kg bw daily to rats as per OECD guidelines 408. After 90 d feeding, heamatological and biochemical parameters of treated rats were compared with control animals. Histopathology of all the major organs was also studied.Results: In the acute toxicity study, no mortality or clinical signs of toxicity were observed in any of the animals at maximum recommended dose level of 2000 mg/kg bw; therefore the LD50 is>2000 mg/kg bw in rats. The repeated administration of PAE for 90 d in rats at the maximum dose level of 1000 mg/kg bw did not induce any observable toxic effects, when compared to its corresponding control animals. The hematology and biochemistry profile of treated rats was similar to control animals and difference was non-significant (p>0.05). The histopathology of major organs of all the control and treated animals was normal. In this study the NOAEL (No Observed Adverse Effect Level) was calculated as 1000 mg/kg bw daily for rats.Conclusion: The present study clearly indicates that PAE does not have any toxic effects in animals at the dose evaluated as evidenced by acute and sub chronic toxicity studies in rats.

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Acute toxicity assessment for TiO2 photocatalyst (GST) made from wastewater using TiCl4 in rat

Environmental Analysis Health and Toxicology ◽

10.5620/eaht.2021019 ◽

2021 ◽

Vol 36 (3) ◽

pp. e2021019

Author(s):

Ja Kyung Seol ◽

Myeongkyu Park ◽

Jae Min Im ◽

Heung Sik Seo ◽

Hee Ju Park ◽

...

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

High Efficiency ◽

Lethal Dose ◽

Clinical Signs ◽

Body Weight Loss ◽

Toxicity Assessment ◽

Female Rats ◽

Sprague Dawley ◽

Weight Changes

TiO2 was a photocatalyst that used to the most common product because of the high efficiency. TiO2 (P-25, commercial nanomaterial product) is the most typical photocatalyst product and TiO2 (GST) was a sludge recycling product. This study was reported to evaluate an acute toxicity of TiO2 (P-25 and GST) according to OECD test guideline 402 and 423 in Sprague-Dawley (SD) female rats via route of oral and dermal. There was investigated the lethal dose (LD50), and mortality, clinical signs, body weight changes and gross findings were continually monitored for 14 days following the single administration. After administration, TiO2 (P-25) was calculated that LD50 was considered to be a dose of over 2000 mg/kg body weight for both different route of exposure, and TiO2 (GST) was the same. Other items were no observed an adverse effect between P-25 and GST; no mortality and clinical signs, accidental body weight loss, no gross findings. On the basis of the above results, the toxicity of the GST was almost equal to that of the commercial product, P-25 and there was no toxicological evidence.

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Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.398 ◽

2018 ◽

Vol 6 (9) ◽

pp. 1581-1587

Author(s):

Sergey A. Zhuchkov ◽

Alexandr S. Kinzirsky ◽

Irina V. Koroleva ◽

Yuriy B. Vicharev

Keyword(s):

Toxic Effect ◽

Adrenal Glands ◽

Clinical Signs ◽

Clinical Manifestations ◽

Repeated Administration ◽

Test Substance ◽

Sprague Dawley ◽

Adverse Effect Level ◽

Pharmacological Substance ◽

Effect Level

BACKGROUND: OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance. AIMS: To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502. MATERIAL AND METHODS: The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg. RESULTS: The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled. CONCLUSION: OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance.

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Nutritional composition, phytochemicals and acute toxicity of herbal mixture (lemon, apple cider, garlic, ginger and honey) in zebrafish embryo and Wistar rat

Food Research ◽

10.26656/fr.2017.4(s1).s11 ◽

2020 ◽

Vol 4 (S1) ◽

pp. 196-204

Author(s):

A. Abu Bakar Sajak ◽

A. Azlan ◽

F. Abas ◽

H. Hamzah

Keyword(s):

Acute Toxicity ◽

Wistar Rats ◽

Zebrafish Embryo ◽

Wistar Rat ◽

Treated Group ◽

Nutritional Composition ◽

Proton Nuclear Magnetic Resonance ◽

Apple Cider ◽

Herbal Mixture ◽

Safe Dose

This study was aimed to provide the reference frame for the safe dose design of polyphenol-rich herbal mixture, which consist of lemon, apple cider, garlic, ginger and honey (PRM) for the future efficacy study. Prior to this, the nutritional composition was first conducted and the identification of metabolites that present in PRM was determined using proton nuclear magnetic resonance (1H-NMR) spectroscopy. The acute toxicity of the PRM was then evaluated in zebrafish embryo and Wistar rats following The Organisation for Economic Co-operation and Development (OECD) guidelines. The PRM nutritional composition and sugar profile showed it was high in carbohydrate, ash and protein and the main sugar is fructose. It also contains metabolites such as fructosefuranose, lactic acid, ascorbic acid, acetic acid, cycloalliin, pyruvate, 5- hydroxymethylfurane, α- and β-glucose. From the zebrafish embryo acute toxicity result, the lethal concentration, LC50 of PRM was at 487.50 μg/mL. Meanwhile, in Wistar rats’ model, no lethality was observed in the group treated with PRM at the end of the study (14 days). No changes were also observed from the behavioural and appetite as well as the biochemical parameters (AST, ALT, total cholesterol, triglyceride, LDL, HDL, total protein and creatinine) of the treated group. Therefore, the safe dose for PRM can be up to 2000 mg/kg b.w. in Wistar rats and below 487.50 μg/mL in zebrafish embryo model.

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A 90-day toxicity and genotoxicity study with high-purity phenylcapsaicin

Toxicology Research and Application ◽

10.1177/2397847318773060 ◽

2018 ◽

Vol 2 ◽

pp. 239784731877306 ◽

Cited By ~ 1

Author(s):

Torbjørn Rage Paulsen ◽

Sebastian Stiller ◽

Klaus Weber ◽

Claudia Donath ◽

Gudrun Schreiband ◽

...

Keyword(s):

Clinical Symptoms ◽

Clinical Chemistry ◽

Human Lymphocytes ◽

Recovery Period ◽

Clinical Signs ◽

Gene Mutations ◽

Oral Gavage ◽

Adverse Effect Level ◽

Dose Oral ◽

Effect Level

To evaluate the safety of the synthetic capsaicin analogue phenylcapsaicin (PheCap; 7-phenylhept-6-yne-acid-hydroxy-3-mathoxylbenzylamide, CAS no 848127-67-3), a 90-day repeated dose oral gavage of 0, 30, 100 or 250 mg/kg body weight (bw)/day toxicity study with a 28-day recovery period was conducted using Wistar rats. Examinations of clinical signs, body and organ weight, haematology, urinalysis, clinical chemistry, food consumption and macroscopic, as well as histopathological tissue examinations were carried out for signs of toxicity. Degenerative, but reversible changes in the liver at 250 mg/kg bw/day, and local irritating effects in the stomach at 100 and 250 mg/kg bw/day were found. These findings were associated with test item-related clinical symptoms, that is, diarrhoea, salivation and moving of bedding material. PheCap did neither cause gene mutations by base pair changes or frame shifts in the genome of the tester stains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 or TA 102 nor induce structural and/or numerical chromosomal damage in human lymphocytes. Therefore, it can be concluded that PheCap is not genotoxic. The No Observed Adverse Effect Level (NOAEL) of PheCap for systemic toxicity is considered to be at 100 mg/kg bw/day which is based on degenerative changes in the liver. Due to irritating effects in the stomach, the NOAEL for local effects was established at 30 mg/kg bw/day.

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LyophilizedB. subtilisZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study in Wistar Rats

Journal of Toxicology ◽

10.1155/2019/3042108 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

B. Appala Naidu ◽

Kamala Kannan ◽

D. P. Santhosh Kumar ◽

John W. K. Oliver ◽

Zachary D. Abbott

Keyword(s):

Body Weight ◽

Wistar Rats ◽

Clinical Signs ◽

Albumin Level ◽

Repeat Dose ◽

Oral Gavage ◽

Toxicological Evaluation ◽

Body Weights ◽

Adverse Effect Level ◽

Dose Oral

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strainB. subtilisZB183. Lyophilized spores at doses of 109, 1010, and 1011 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days.B. subtilisZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010and 1011 CFU/kg/day doses without an increase in total protein in males or females and was considered a nonadverse effect. The “No Observed Adverse Effect Level (NOAEL)” is defined at the highest dose of 1011 CFU/kg body weight/day for lyophilizedB. subtilisZB183 Spores under the test conditions employed.

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The Oral NOAEL of Flurochloridone in Male Wistar Rats in Ninety-Day Subchronic Toxicity Test Was 3mg/kg/day

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16040553 ◽

2019 ◽

Vol 16 (4) ◽

pp. 553 ◽

Cited By ~ 2

Author(s):

Hongyan Zhu ◽

Rui Li ◽

Su Zhou ◽

Suhui Zhang ◽

Yu Wang ◽

...

Keyword(s):

Adverse Effect ◽

Wistar Rats ◽

Serum Testosterone ◽

Male Rats ◽

Subchronic Toxicity ◽

Sperm Abnormalities ◽

Testicular Weight ◽

Adverse Effect Level ◽

Male Wistar Rats ◽

Effect Level

A ninety-day toxicity and toxicokinetics of flurochloridone (FLC) were studied in male Wistar rats with oral administration at doses of 3 mg/kg and 10 mg/kg respectively, following the previous study. Apparent toxicity to reproductive system of male rats was still observed at the dose of 10 mg/kg, trace amounts of FLC were still detected 24 hours after administration, testicular weight, epididymal weight and serum testosterone were significantly reduced and sperm abnormalities in epididymis were significantly increased. No abnormalities were found in 3 mg/kg group, it indicated that no-observed-adverse-effect level (NOAEL) of FLC in male rats was 3 mg/kg/day, far below the dose of 20 mg/kg/day reported by European Food Safety Authority (EFSA). Therefore, more attention should be paid to this herbicide.

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