Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single and Repeated Oral Dose Toxicity and Genotoxicity of the Leaves of Butterbur.

ABSTRACT: 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.

SUBMITTER: Park S

PROVIDER: S-EPMC8394925 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Assessment of the 4-week repeated-dose oral toxicity and genotoxicity of GHX02.

Project description:Herbal medicines are widely utilized for disease prevention and health promotion. GHX02 consists of mixtures including Gwaruin (Trichosanthes kirilowii), Haengin (Prunus armeniaca), Hwangryeon (Coptis japonica) and Hwangkeum (Scutellaria baicalensis). It has been purported to have therapeutic effectiveness in cases of severe bronchitis. Non-clinical safety testing comprised a single-dose oral toxicity study and a 28-day repeated-dose oral toxicity study with a 14-day recovery period, and genotoxicity was assessed by a bacterial reverse mutation test, in vitro chromosomal aberration test, in vivo mouse bone marrow micronucleus test and single cell gel electrophoresis assay (comet assay). In the single-dose oral toxicity study, the approximate lethal dosage is estimated to be higher than 5000 mg/kg in rats. Thus, the dosage levels were set at 0, 1250, 2500 and 5000 mg/kg/day in the 28-day repeated-dose oral toxicity study, and 10 male rats and 10 female rats/dose were administered GHX02. No clinical signs of toxicological significance were recorded in any animal during the dosing and the observation period in the single-dose study. The no-observed-adverse-effect level of GHX02 was 5000 mg/kg/day when administered orally for 28 days to male and female Sprague-Dawley rats. Despite increases in the frequencies of cells with numerical chromosomal aberration in the in vitro test, the increases were not considered relevant to the in vivo genetic risk. Except for the increase of in vitro numerical chromosomal aberration, clear negative results were obtained from other genetic toxicity studies.

| S-EPMC7004199 | biostudies-literature

Genotoxicity and repeated-dose toxicity evaluation of dried <i>Wolffia globosa</i> Mankai.

Project description:Wolffia is a genus of protein-rich aquatic plants. Mankai, a cultivated strain of Wolffia globosa, contains more than 40 % protein based on dry matter evaluation. Furthermore, Mankai is nutritionally excellent as a food material, and is expected to be applicable to various products as a substitute for animal protein. A battery of toxicological studies was conducted on the dried product of Mankai (Dry Mankai), with the expectation to utilize it as a raw material for food applications. Dry Mankai was not genotoxic in a bacterial reverse mutation test and in vitro micronucleus assay. In the subchronic toxicity study, rats were provided Dry Mankai in the diet at levels of 0 %, 5 %, 10 %, or 20 % (w/w), equivalent to 0, 3.18, 6.49, and 13.16 g/kg/day for males and 0, 3.58, 7.42, and 15.03 g/kg/day for females, respectively. No adverse effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and blood chemistry, urinalysis, and macroscopic and microscopic findings. According to the repeated-dose study in rats, the no observed adverse effect level of Dry Mankai was 20 % (w/w) for both sexes (13.16 and 15.03 g/kg/day for males and females, respectively).

| S-EPMC7505750 | biostudies-literature

<i>In vitro</i> genotoxicity assessment and 28-day repeated dose oral toxicity study of steady-calcium formula in rats.

Project description:Steady-calcium formula (SCF), a functional food mixture with potential of joint care, contains five major ingredients. However, the uncertain cross-reactivity among these included ingredients cannot be excluded. Hence, it is important to ensure the safety of this mixture. In this study, the safety of SCF was evaluated through in vitro genotoxicity assessment and 28-day oral toxicity study in rats. The bacterial reverse mutation test and mammalian chromosome aberration test displayed that SCF did not induce mutagenicity and clastogenicity. The 28-day repeated dose assessment of SCF in rats revealed no mortality and adverse effects in clinical signs, body weight, urinalysis, hematology, organ weight, and histopathology at all treated groups. Although some significant changes were observed in food intake and parameters of serum biochemistry at the highest dose in males, they were not dose-related and considered to be within normal range. These findings indicate that SCF does not possess genotoxic potential and no obvious evidence of subacute toxicity. These results demonstrate for the first time that the genotoxicity and subacute toxicity for SCF are negative under our experimental conditions and the no observed adverse effect level (NOAEL) of SCF may be defined as at least 5470 mg/kg/day.

| S-EPMC9742816 | biostudies-literature

Validation study of the combined repeated-dose toxicity and genotoxicity assay using gpt delta rats.

Project description:Transgenic rodents carrying reporter genes to detect organ-specific in vivo genetic alterations are useful for risk assessment of genotoxicity that causes cancer. Thus, the Organization for Economic Co-operation and Development has established the guideline for genotoxicity tests using transgenic animals, which may be combined with repeated-dose toxicity studies. Here, we provide evidence to support equivalence of gpt delta and wild type (WT) rats in terms of toxicological responses to a genotoxic hepatocarcinogen, N-nitrosodiethylamine (DEN), and a non-genotoxic hepatocarcinogen, di(2-ethylhexyl)phthalate (DEHP). gpt delta rats treated with DEHP showed similar increases in liver and kidney weights, serum albumin, albumin/globulin ratios, and incidence of diffuse hepatocyte hypertrophy compared to WT F344 and Sprague-Dawley (SD) rats. DEN-treated gpt delta rats showed equivalent increases in the number and area of precancerous GST-P-positive foci in the liver compared to WT rats. The livers of DEN-treated gpt delta rats also showed increased frequencies of gpt and Spi(-) mutations; such changes were not observed in DEHP-treated gpt delta rats. These results indicated that gpt delta rats (both F344 and SD backgrounds) showed comparable DEHP-induced toxicity and DEN-induced genotoxicity to those observed in WT rats. With regard to the administration period, the general toxicity of 1.2% DEHP was evident throughout the experimental period, and the genotoxicity of 10 p.p.m. DEN could be detected after 2 weeks of administration and further increased at 4 weeks. These results suggested that combined assays using gpt delta rats could detect both general toxicity and genotoxicity by the canonical 4-week administration protocol. Therefore, this assay using gpt delta rats would be applicable for risk assessment including early detection of genotoxic carcinogens and ultimately serve to reduce cancer risks in humans from environmental chemicals.

| S-EPMC4452153 | biostudies-literature

Oral repeated-dose toxicity studies of coenzyme Q10 in beagle dogs.

Project description:To support phase III testing of coenzyme Q10 (CoQ₁₀) in humans, we conducted pharmacokinetic and toxicology studies in beagle dogs. Following single gavage administration of CoQ₁₀ at 600, 1200, 1800, or 2400 mg/kg per d no obvious dose response was observed in maximum concentration (C(max)) or area under the curve (AUC) versus time curve at the 3 highest dosages. In a repeated-dose study of CoQ₁₀ at 600, 1200, 1800, or 2400 mg/kg per d for 4 weeks, CoQ₁₀ reached steady state in plasma by 2 weeks at all dosages. Both C (max) and AUC increased with increasing dosage of CoQ₁₀. The highest plasma levels were recorded at 1800 mg/kg per d. In a 39-week chronic toxicity study of CoQ₁₀ at 1200 and 1800 mg/kg per d or placebo, CoQ₁₀ reached steady state in plasma by 13 weeks. Behaviors, blood chemistries, and detailed histopathology were normal. No deaths occurred. These results support the use of a 2400 mg/d dosage of CoQ₁₀ in human clinical trials.

| S-EPMC3288259 | biostudies-literature

Investigation of repeated dose (90 day) oral toxicity, reproductive/developmental toxicity and mutagenic potential of 'Calebin A'.

Project description:The present work investigated repeated dose and reproductive toxicity of Calebin A in Wistar rats. A study for assessing the mutagenic potential of Calebin A through an AMES test is also described. Calebin A was orally administered to groups of 10 male and/or 10 female Wistar rats each, assigned to three dose levels (20, 50 and 100 mg/kg/body weight) once daily for 90 consecutive days. None of the animals in any of the treatment/control groups exhibited any abnormal clinical signs/behavioral changes, reproductive as well as developmental parameters, or gross and microscopic changes in both male and female rats. Calebin A was also evaluated for its ability to induce reverse mutations at selected loci of Salmonella typhimurium in the presence and absence of Aroclor 1254 induced rat liver S9 cell lines. In conclusion, 100 mg/kg/d of Calebin A is not likely to produce any significant toxic effects in male and female Wistar rats and no reproductive or developmental toxicity was observed at the same dose and hence Calebin A at 100 mg/kg was determined as "No Observed Adverse Effect Level (NOAEL)" under the test conditions.

| S-EPMC5598428 | biostudies-literature

In Vitro, Oral Acute, and Repeated 28-Day Oral Dose Toxicity of a Mixed-Valence Polyoxovanadate Cluster.

Project description:Polyoxovanadates (POV) are a subgroup of polyoxometalates (POM), which are nanosized clusters with reported biological activities. This manuscript describes the first toxicity evaluation of a mixed-valence polyoxovanadate, pentadecavanadate, (Me4N)6[V15O36Cl], abbreviated as V15. Cytotoxicity experiments using peripheral blood mononuclear cells (PBMC), larvae of Artemia salina Leach, and in vivo oral acute and repeated 28-day doses in mice was carried out. The LC50 values in PBMC cells and A. salina were 17.5 ± 5.8 μmol L-1, and 17.9 µg L-1, respectively, which indicates high cytotoxic activity. The toxicity in mice was not observed upon acute exposure in a single dose, however, the V15 repeated 28-day oral administration demonstrated high toxicity using 25 mg/kg, 50 mg/kg and, 300 mg/kg doses. The biochemical and hematological analyses during the 28-day administration of V15 showed significant alteration of the metabolic parameters related to the kidney and liver, suggesting moderate toxicity. The V15 toxicity was attributed to the oxidative stress and lipid peroxidation, once thiobarbituric acid (TBAR) levels significantly increased in both males and females treated with high doses of the POV and also in males treated with a lower dose of the POV. This is the first study reporting a treatment-related mortality in animals acutely administrated with a mixed-valence POV, contrasting with the well-known, less toxic decavanadate. These results document the toxicity of this mixed-valence POV, which may not be suitable for biomedical applications.

| S-EPMC10536805 | biostudies-literature

26-Week Repeated Dose Oral Toxicity Study of KCHO-1 in Sprague-Dawley Rats.

Project description:Objectives:KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. Methods:Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. Results:Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. Conclusion:NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

| S-EPMC6820473 | biostudies-other

Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats.

Project description:Background:Ursolic acid (UA) has been used in alternative medicine for decades, and there has been a great interest in its medicinal properties. Despite this increased interest, a detailed long-term toxicity study has not been performed. The objective of this study was to determine the long-term toxic effect of UA on clinical chemistry, haematology, coagulation, pathology/morphology, behaviour and motor skills in rats. Methods:A solution was made by dissolving UA in a mixture of 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose in Milli-Q Water. The control group received the vehicle, and the test groups received a dose up to 1000?mg/kg/day via oral gavage. The solution was administered to both male and female (Han-Wistar) rats for 90 consecutive days. Results:UA did not cause any deaths, abnormal body weights or abnormal pathology at all test doses. In addition to that, no toxicological changes were observed in behaviour, neurotoxicity, coagulation, haematology or clinical chemistry that are related to the administration of UA. Conclusion:This study indicates that oral dosing of UA for 90 consecutive days does not lead to toxic effects at any of the doses. Therefore, the NOAEL for UA is likely to be higher than 1000?mg/kg/day.

| S-EPMC7229404 | biostudies-literature

Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice.

Project description:6:2 fluorotelomer alcohol (6:2 FTOH) was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL) for systemic toxicity was 25 mg/kg/day (males) and 5 mg/kg/day (females), based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell), clinical chemistry (liver-related), liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland). However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

| S-EPMC5598097 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data