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

ABSTRACT: 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.

SUBMITTER: Geerlofs L

PROVIDER: S-EPMC7229404 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Geerlofs Lotte L He Zhiyong Z Xiao Sa S Xiao Zhi-Cheng ZC

Toxicology reports 20200508

<h4>Background</h4>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.<h4>Methods</h4>A solution was made by dissolving UA in a mixture of 0 ...[more]

PMID: 32435599

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Project description:BackgroundNanotechnology is indispensable to many different applications. Although nanoparticles have been widely used in, for example, cosmetics, sunscreen, food packaging, and medications, they may pose human safety risks associated with nanotoxicity. Thus, toxicity testing of nanoparticles is essential to assess the relative health risks associated with consumer exposure.MethodsIn this study, we identified the NOAEL (no observed adverse effect level) of the agglomerated/aggregated TiO2 P25 (approximately 180 nm) administered at repeated doses to Sprague-Dawley (SD) rats for 28 and 90 days. Ten of the 15 animals were necropsied for toxicity evaluation after the repeated-dose 90-day study, and the remaining five animals were allowed to recover for 28 days. The agglomerated/aggregated TiO2 P25 dose levels used included 250 mg kg- 1 d- 1 (low), 500 mg kg- 1 d- 1 (medium), and 1000 mg kg- 1 d- 1 (high), and their effects were compared with those of the vehicle control. During the treatment period, the animals were observed for mortality, clinical signs (detailed daily and weekly clinical observations), functional observation battery, weekly body weight, and food and water consumption and were also subjected to ophthalmological examination and urinalysis. After termination of the repeated-dose 28-day, 90-day, and recovery studies, clinical pathology (hematology, blood coagulation time, and serum biochemistry), necropsy (organ weights and gross findings), and histopathological examinations were performed.ResultsNo systemic toxicological effects were associated with the agglomerated/aggregated TiO2 P25 during the repeated-dose 28-day, 90-day, and recovery studies in SD rats. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg kg- 1 d- 1, and the substance was not detected in the target organs.ConclusionSubacute and subchronic oral administration of the agglomerated/aggregated TiO2 P25 was unlikely to cause side effects or toxic reactions in rats.

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

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

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