scholarly journals A Toxicological Evaluation of Germanium Sesquioxide (Organic Germanium)

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Robin A. Reddeman ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Timothy S. Murbach ◽  
Gábor Hirka ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Germanium Dioxide ◽  
Oral Toxicity ◽  
Toxicological Evaluation ◽  
Toxicological Studies ◽  
Adverse Effect Level ◽  
Dose Oral ◽  
Chromosomal Aberration Test

A battery of OECD- and GLP-compliant toxicological studies was performed to assess the safety of a highly purified germanium sesquioxide, an organic form of the naturally occurring, nonessential trace element germanium. Germanium dioxide and germanium lactate citrate (inorganic germaniums) have been shown to induce renal toxicity, whereas germanium sesquioxide (an organic germanium) has been shown to have a more favorable safety profile. However, past toxicity studies on germanium sesquioxide compounds have not clearly stated the purity of the tested compounds. In the studies reported herein, there was no evidence of mutagenicity in a bacterial reverse mutation test or an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/day. In a 90-day repeated-dose oral toxicity study in Han:WIST rats conducted at doses of 0, 500, 1000, and 2000 mg/kg bw/day by gavage, there were no mortalities, treatment-related adverse effects, or target organs identified. The no-observed-adverse-effect-level (NOAEL) was determined to be 2000 mg/kg bw/day.

scholarly journals An Evaluation of the Genotoxicity and Subchronic Oral Toxicity of Synthetic Curcumin

2018 ◽  
Vol 2018 ◽  
pp. 1-27 ◽  
Author(s):  
Sreenivasa Rao Damarla ◽  
Rajesh Komma ◽  
Upendra Bhatnagar ◽  
Navin Rajesh ◽  
Sadik Mohmad Abdulhamid Mulla
Keyword(s):  
Micronucleus Test ◽  
Repeated Dose ◽  
Oral Toxicity ◽  
Split Dose ◽  
Toxicological Studies ◽  
Adverse Effect Level ◽  
Dose Oral ◽  
Chromosomal Aberration Test

A battery of toxicological studies was conducted in accordance with international guidelines to investigate the genotoxicity and repeated-dose oral toxicity in rats of synthetic curcumin (VEAMIN 99, >99% purity). There was no evidence of mutagenicity in a bacterial reverse mutation test, whereas an in vitro mammalian chromosomal aberration test was positive for induction of chromosomal aberrations which is in line with results reported for natural curcumin. There was no evidence of genotoxicity in an in vivo mammalian micronucleus test. Synthetic curcumin did not cause mortality or toxic effects in a 90-day repeated-dose oral toxicity study at daily doses of 250, 500, or 1000 mg/kg body weight (bw)/day (administered by gavage in a split dose). The no observed adverse effect level (NOAEL) determined from the 90-day study was 1000 mg/kg bw/day for both male and female Wistar rats.

scholarly journals A Toxicological Assessment of Creatyl-l-Leucine

2018 ◽  
Vol 37 (2) ◽  
pp. 171-187 ◽  
Author(s):  
Robin A. Reddeman ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Timothy S. Murbach ◽  
Gábor Hirka ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Female Rats ◽  
Repeated Dose ◽  
Oral Toxicity ◽  
Synthetic Compound ◽  
Male And Female Rats ◽  
Toxicological Studies ◽  
Dose Oral

A battery of toxicological studies was conducted to investigate the genotoxicity and repeated-dose oral toxicity of creatyl-l-leucine, a synthetic compound, in rats in accordance with internationally accepted guidelines. There was no evidence of mutagenicity in a bacterial reverse mutation test and in an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2,000 mg/kg bw/d. Creatyl-l-leucine did not cause mortality or toxic effects in Hsd.Han Wistar rats in a 90-day repeated-dose oral (gavage) toxicity study at doses of 1,250, 2,500, and 5,000 mg/kg bw/d. The no observed adverse effect level from the 90-day study was determined to be 5,000 mg/kg bw/d, the highest dose tested, for both male and female rats.

scholarly journals A Toxicological Evaluation of Mango Leaf Extract (Mangifera indica) Containing 60% Mangiferin

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Robin A. Reddeman ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Amy E. Clewell ◽  
Gábor Hirka ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Micronucleus Test ◽  
Mangifera Indica ◽  
Female Rats ◽  
Oral Toxicity ◽  
Toxicological Evaluation ◽  
Male And Female Rats ◽  
Toxicological Studies

A battery of OECD- and GLP-compliant toxicological studies was performed on mango leaf extract (Mangifera indica) containing 60% mangiferin (MLE). No evidence of genotoxicity was found in a bacterial reverse mutation test (Ames). While evidence of clastogenic activity was noted in an in vitro chromosomal aberration test, an in vivo mammalian micronucleus test showed no findings up to the limit dose (2000 mg/kg bw). A 90-day repeated dose oral toxicity study was conducted in rats using doses of 0 (vehicle control), 500, 1000, and 2000 mg/kg bw/day. Based on the lack of mortality or toxic effects in the 90-day study, the NOAEL for MLE in Han:Wist male and female rats was determined to be 2000 mg/kg bw/day, the highest dose tested.

scholarly journals A Toxicological Evaluation of a Standardized Hydrogenated Extract of Curcumin (CuroWhite™)

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Alastimmanahalli Narasimhiah Ravikumar ◽  
Joby Jacob ◽  
Sreeraj Gopi ◽  
Tumkur Subbarao Jagannath
Keyword(s):  
Test Item ◽  
Micronucleus Test ◽  
Repeated Dose ◽  
High Dose ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Evaluation ◽  
Chromosomal Aberration Test

A series of toxicological investigations were conducted in order to evaluate the genotoxic potential and repeated-dose oral toxicity of CuroWhite, a proprietary extract of curcumin that has been hydrogenated and standardized to not less than 25% hydrogenated curcuminoid content. All tests were conducted in general accordance with internationally accepted standards. The test item was not mutagenic in the bacterial reverse mutation test or in vitro mammalian chromosomal aberration test, and no in vivo genotoxic activity was observed in rat bone marrow in the micronucleus test. A 90-day repeated-dose study was conducted in male and female Sprague-Dawley rats. Two mortalities occurred in the main and satellite high-dose groups and were determined due to gavage error. No organ specific or other toxic effects of the test item were observed up to the maximum dose of 800 mg/kg bw/day, administered by gavage. NOAEL was, therefore, estimated as 800 mg/kg bw/day.

scholarly journals Toxicological Evaluation of a Mixture of Astragalus membranaceus and Panax notoginseng Root Extracts (InnoSlim®)

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Timothy S. Murbach ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Gábor Hirka ◽  
Adél Vértesi ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Panax Notoginseng ◽  
Astragalus Membranaceus ◽  
Human Consumption ◽  
Oral Toxicity ◽  
Toxicological Evaluation ◽  
Root Extracts ◽  
Dose Oral ◽  
History Of

Astragalus spp. and Panax spp. have a long history of traditional human use. A blend, InnoSlim®, of highly purified and fractionated root extracts from Astragalus membranaceus and Panax notoginseng has now been developed for human consumption; however, the unique constituent content of this blend has not been specifically evaluated with respect to safety. Therefore, the toxicological potential of the blend was formally investigated in a series of studies—genetic toxicity was evaluated in a bacterial reverse mutation test followed by an in vivo mammalian micronucleus test, and general toxicity was evaluated in a 28-day repeated-dose oral toxicity study in rats. No evidence of mutagenicity was observed in the bacterial tester strains used, and no evidence of in vivo chromosomal damage resulting in increased frequency of micronucleated cells was observed in male Crl:NMRI BR mice. No mortality or toxic effects were observed, and no target organs were identified, in male and female Han:WIST rats exposed to 0, 400, 800, or 1200 mg/kg bw/day of the blend by gavage for 28 consecutive days. The highest dose—1200 mg/kg bw/day—was determined to be the NOAEL. Based on these results, extrapolation towards a safe human consumption level can be explored.

scholarly journals A Toxicological Evaluation of Chlamydomonas reinhardtii, a Green Algae

2018 ◽  
Vol 37 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Timothy S. Murbach ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Gábor Hirka ◽  
Adél Vértesi ◽  
...  
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Green Algae ◽  
Micronucleus Test ◽  
Repeated Dose ◽  
Continuous Exposure ◽  
Oral Toxicity ◽  
Food Ingredient ◽  
Toxicological Evaluation ◽  
Dose Oral

There is a current worldwide interest in developing novel sustainable nonanimal nutritional sources, and one such source is the green algae Chlamydomonas reinhardtii, the only green algae that has been studied as a model organism for many biological processes ranging from photosynthesis to flagellar movement. However, its potential as a safe nutritional source for use in various foods has not been thoroughly investigated. To assess the safety of C reinhardtii for use as a nutritional human food ingredient, in accordance with internationally accepted standards, the genotoxic potential and repeated-dose oral toxicity of the dried C reinhardtii (THN 6) algal biomass was investigated. The following studies were conducted: (1) a bacterial reverse mutation test, (2) an in vitro mammalian chromosomal aberration test, (3) an in vivo mammalian micronucleus test, and (4) a 28-day repeated-dose oral toxicity study in rats. No evidence of mutagenicity or genotoxic activity was observed in the first 3 tests under the applied test systems. In the 28-day study, male and female Hsd.Han Wistar rats were exposed to daily doses of 0, 1,000, 2,000, and 4,000 mg/kg bw by gavage. Following 28 days of continuous exposure, no mortality or treatment-related adverse effects were observed and no target organs were identified. Therefore, a no observed adverse effect level was concluded as 4,000 mg/kg bw/day, the highest dose tested.

scholarly journals Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini
Keyword(s):  
Rattus Norvegicus ◽  
Bone Marrow Cells ◽  
Micronucleus Test ◽  
Term Treatment ◽  
Genotoxic Effects ◽  
Short Term ◽  
Short Term Treatment ◽  
Chromosomal Aberration Test

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

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.

Absence of Mutagenicity, Genotoxicity, and Subchronic Oral Toxicity of Touchi Extract

2007 ◽  
Vol 26 (5) ◽  
pp. 465-473 ◽  
Author(s):  
Hiroyuki Fujita ◽  
Tomohide Yamagami
Keyword(s):  
Micronucleus Test ◽  
Clinical Signs ◽  
Water Extract ◽  
Human Consumption ◽  
Mouse Bone Marrow ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Toxicological Studies ◽  
Chinese Food

Touchi, a traditional Chinese food used mainly for seasoning is obtained by first steaming soybeans followed by fermentation with Aspergillus oryzae (koji). A series of toxicological studies was conducted to evaluate the mutagenic and genotoxic potential and subchronic toxicity of a water extract of Touchi, a known inhibitor of α-glucosidase activity. Touchi extract (TE) did not induce reverse mutations in Salmonella typhimurium strains TA98, TA1537, TA100, TA1535, and Escherichia coli WP2uvrA at concentrations up to 5000 μg/plate, in either the absence or presence of exogenous metabolic activation. No deaths occurred and no abnormal clinical signs were observed in any animal in any group in an in vivo micronucleus test, and TE was devoid of clastogenic activity when administered orally to mice at doses up to 2000 mg/kg/day. Thus, TE was evaluated as negative in the bacterial reverse mutation and mouse bone marrow micronucleus tests under the conditions of these assays. To evaluate its subchronic toxicity, SPF rats were administered TE at doses of 0,250,1000, and 2500 mg/kg/day via oral gastric intubation. No treatment-related toxic changes were seen in clinical signs, body weight, food consumption, urinalysis, hematology, blood chemistry, necropsy, organ weight, or histopathology. The no observed adverse effect level for TE was thus considered to be more than 2500 mg/kg/day in both males and females. These results are consistent with Touchi’s status as a traditional Chinese food derived from fermented soybeans and its purported long history of use. Specifically, these data are consistent with the expected safety of human consumption of TE up to at least 5 g/day.

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