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 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 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 Comprehensive Toxicological Safety Assessment of an Extract of Olea Europaea L. Leaves (Bonolive™)

2015 ◽  
Vol 35 (2) ◽  
pp. 208-221 ◽  
Author(s):  
Amy E. Clewell ◽  
Erzsébet Béres ◽  
Adél Vértesi ◽  
Róbert Glávits ◽  
Gábor Hirka ◽  
...  
Keyword(s):  
Olea Europaea ◽  
Water Soluble ◽  
Female Rats ◽  
Repeated Dose ◽  
Oral Toxicity ◽  
Olea Europaea L ◽  
Male And Female Rats ◽  
Toxicological Studies ◽  
Dose Oral ◽  
Olea Europaéa

A battery of toxicological studies was conducted to investigate the genotoxicity and repeated-dose oral toxicity of Bonolive™, a proprietary water-soluble extract of the leaves of the olive tree ( Olea europaea L.), in accordance with internationally accepted protocols. There was no evidence of mutagenicity in a bacterial reverse mutation test and in an vitro mammalian chromosomal aberration test nor was any genotoxic activity observed in an in vivo mouse micronucleus test at concentrations up to the limit dose of 2000 mg/kg bw/d. Bonolive™ did not cause mortality or toxic effects in Crl:(WI)BR Wistar rats in a 90-day repeated-dose oral toxicity study at doses of 360, 600, and 1000 mg/kg bw/d. The no observed adverse effect level in the 90-day study was 1000 mg/kg bw/d for both male and female rats, the highest dose tested.

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 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 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.

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

2014 ◽  
Vol 307 (4) ◽  
pp. H504-H514 ◽  
Author(s):  
K. Tarhouni ◽  
M. L. Freidja ◽  
A. L. Guihot ◽  
E. Vessieres ◽  
L. Grimaud ◽  
...  
Keyword(s):  
Blood Flow ◽  
Female Rats ◽  
Male Rats ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Male And Female ◽  
Male And Female Rats ◽  
Arterial Contractility

In resistance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3- and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.

Effect of age on the 3,5,3′-tri-iodothyronine-induced increase in sugar uptake in rat thymocytes

1986 ◽  
Vol 110 (3) ◽  
pp. 511-515 ◽  
Author(s):  
J. Segal ◽  
B. R. Troen
Keyword(s):  
Female Rats ◽  
In Vivo Studies ◽  
Sugar Uptake ◽  
Male And Female Rats ◽  
Old Rats ◽  
Effect Of Age ◽  
Age And Sex ◽  
In Cells

ABSTRACT The effect of age on the responsiveness of rat thymocytes to 3,5,3′-tri-iodothyronine (T3) was studied. It has been demonstrated previously that the plasma membrane-mediated effect of T3 to increase sugar uptake by rat thymocytes is influenced by age and sex. In both sexes, T3 given in vitro stimulated sugar uptake in cells from animals of 15 days of age, had no effect at 21 days and was again effective at 26 days. In the male, thymocytes from animals of 40 days of age and older were refractory to T3. However, in the female, T3, although less effective than in cells from 26-day-old animals, remained stimulatory in cells from 40- and 60-day-old rats. T3 had no effect in cells from animals of 90 days of age and older. In in-vivo studies in which female rats of 26, 60 and 90 days of age were first injected with T3 and 1 h later with [3H]2-deoxyglucose, the responsiveness of thymocytes to T3 also declined progressively with advancing age; T3 was most effective in cells from 26-day-old animals, less stimulatory in 60-day-old and essentially without effect in cells from 90-day-old animals. From these observations we have concluded that in both male and female rats the responsiveness of thymocytes to T3 declines progressively with age, and that this decline occurs at an earlier age in cells obtained from males. J. Endocr. (1986) 110, 511–515

scholarly journals Single and Repeated Oral Dose Toxicity and Genotoxicity of the Leaves of Butterbur

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1963
Author(s):  
Sangsu Park ◽  
Jeongin Lim ◽  
Kyung Tae Lee ◽  
Myung Sook Oh ◽  
Dae Sik Jang
Keyword(s):  
Oral Dose ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Hot Water ◽  
Female Rats ◽  
Human Consumption ◽  
In Vitro Tests ◽  
Male And Female Rats

Butterbur (Petasites japonicus (Siebold & Zucc.) Maxim) leaves are available to consumers in the marketplace, but there is no guarantee that they are safe for human consumption. Previously, we demonstrated that hot water extracts of P. japonicus leaves (KP-1) had anti-inflammatory properties and attenuated memory impairment. However, data regarding KP-1 toxicity are lacking. This study assessed the safety of KP-1 by examining oral and genotoxic effects using in vivo and in vitro tests, respectively. In a single oral dose toxicity and two-week repeated oral dose toxicity study, we observed no toxicologically significant clinical signs or changes in hematology, blood chemistry, and organ weights at any dose during the experiment. Following a thirteen-week repeated oral dose, toxicity, hyperkeratosis, and squamous cell hyperplasia of the limiting ridge in the stomach were observed. The no observable adverse effect level (NOAEL) was found to be 1250 mg/kg/day in male and female rats. However, hyperkeratosis and hyperplasia were not considered to be of toxicological significance when extrapolating the NOAEL to humans because the limiting ridge in the stomach is species-specific to rats. Therefore, in our study, the NOAEL was considered to be 5000 mg/kg/day when the changes in the stomach’s limiting ridge were discounted. Moreover, in vitro bacterial reverse mutations and chromosomal aberrations in Chinese hamster lung (CHL) cells and the in vivo micronucleus in Institute of cancer research (ICR) mice assays showed that KP-1 possessed no mutagenicity. Although additional research is required, these toxicological evaluations suggest that KP-1 could be safe for human consumption.

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