Subchronic Toxicity Study Research Articles

Toxicity Assessment of Ethanol Extract of Saussurea lappa (Costus) Root in Male Wistar Rats

: Background and Objective: Saussurea lappa is a medicinal plant that has been used in the treatment of various disease conditions for decades. Researchers have provided diversified characteristics of this medicinal plant, enormous data about the bioactive compounds and as well its pharmacological properties. However, information regarding toxicity study of Saussurea lappa root is lacking. The acute and sub-chronic toxicity of Saussurea lappa root ethanolic extract was investigated in this study using an in vivo model (male Wistar rats). Materials and Method: The acute toxicity study was done in two phases: Phase One comprised four groups of three rats each which were administered with 50 mg, 100 mg and 1600 mg per kg bodyweight ethanolic extract of S. lappa while the last group (control) was given water and normal fed once. Phase Two involved administering 1600 mg, 2900 mg and 5000 mg per bodyweight. The median lethal dose of the plant was determined in the acute toxicity study. In sub-chronic toxicity studies, the effects of S. lappa root ethanol extract in daily single oral administration at the doses of 200, 400 and 800 mg/kg during 28 days were determined. The blood haematological and biochemical parameters as well as the histopathological examination of the liver and kidneys were studied. Results: In acute study, a single administration of the Saussurea lappa root ethanolic extract up to a dose of 5000 mg/kg did not cause mortality of animals all through the study. Thus, the median lethal dose (LD50) of Saussurea lappa root ethanolic extract was greater than 5000 mg/kg. Saussurea lappa root ethanolic extract caused no significant effect in the haematological and biochemical parameters of the treated groups when compared to the control. There were also no noticeable histological changes in the liver and kidneys of the Saussurea lappa treated rats compared to controls.. Conclusion: These results have shown that oral administration of Saussurea lappa root ethanol extract did not yield any significant toxic effect when acutely and daily administered for 28 days in the male Wistar rats. Hence, Saussurea lappa root ethanol extract could be regarded as a safe natural product for therapeutic use.

The Acute and Subchronic Toxicity Evaluation of methanol leaf Extracts Of Bombaxbuonopozense

Natural products serve as the foundation for conventional medicine and are significant sources of lead compounds for medication research. One of the underutilized plants in West Africa is Bombax buonopozense. West African populations use the majority of its parts for nutritional and therapeutic purposes. The research was aimed at evaluation of the Acute and subchronic oral toxicity of Bombaxbuonopozense leaves extract in rats.In the acute toxicity study, female rats received oral doses of 2000 mg/kg of Bombaxbuonopozense extract (n = 5/group). Abnormal behavior, toxic symptoms, weight changes, and mortality were monitored for 14 consecutive days to evaluate acute toxicity. For the sub-chronic toxicity study, the extract was orally administered to Wistar rats at doses of 800 and 1600 mg/kg (n = 5/group) daily for 28 days. Daily observations were made on the general behavior and body weight of the rats. Biochemical and hematological analyses were performed at the end of the treatment period. Following acute oral administration, the LD50 of Bombaxbuonopozens leaves extract was found to be greater than 2000 mg/kg in the evaluation of acute oral toxicity. Administration of Bombaxbuonopozense extract to rats did showed significantly increase in platelate in the treated group (362.00±23.67*) when compared to the control group (451.67±30.77) at (p>0.05). The liver enzymes, An increase (P>0.05) was seen in ALP concentration on the treated group (216.59±44.29*) In the subchronic oral toxicity assessment at doses of 800 and 1600 mg/kg/day for 28 days, no significant changes were observed in food consumption, body weight gain, organ weights, and biochemical parameters. Treatment of rats with Bombaxbuonopozense extract showed a significant increase in ALP on the group treated with 1600 mg/kg (216.59±44.29*) compared to the control (98.70±13.32) and significant increase in LDL for the treated groups 800 mg/kg (70.76±8.19*) and 1600 mg/kg (71.40±13.17*) were observed when compared with.The current research demonstrated that administration of Bombaxbuonopozense extract orally for 28 days, at doses of up to 1600 mg/kg, did not cause any toxic effects. Based on the acute toxicity study, the estimated median lethal dose (LD50) of the extract was more than 2000 mg/kg.

Toxicological evaluation of LivLonga®, a polyherbal combination, in rodents

There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about Curcuma longa, Garcinia indica and Piper nigrum which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga® is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga® using in vivo models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga® showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.

The Development of a Novel Nanoherbal Passionfruit (Passiflora edulis) Leaves with Safety and Analgesic Effect

Passionfruit (Passiflora edulis) leaves are proven to contain flavonoids especially quercetin and showed a significant antinociceptive effect at acetic acid-induced wriggling. Modification of passionfruit leaf extract into nanoparticles can provide therapeutic effects precisely, quickly, and optimally. This study aimed to provide the method of preparation, and characterization of nanoherbal passionfruit leaves (NPL) and evaluate its safety profiles and analgesic effect. NPL was synthesized using ionic gelation methods, with 3 formula variations. Passionfruit leaf extract was dissolved using mixed solvents. The passionfruit leaves extract solution was suspended in Chitosan and dripped with sodium tripolyphosphate solution until nanoparticle formation. The characterization of the NPL study was evaluated by measuring the particle size, polydispersity index (PI), zeta potential, entrapment efficiency (EE), drug release, and transmission electron microscope (TEM) images. The safety profiles of NPL were then assessed in mice by acute and subchronic toxicity using OECD methods. The effectiveness of NPL as an analgesic was tested using an acetic acid test (visceral pain) in mice. We found the particle size of the NPL’s best formula (F2-NPL) obtained was 187.6 nm with polydispersity index 0.626 and zeta potential +31.2 mV. The entrapment efficiency of flavonoid content in NPL was 50.9 % and the flavonoid release for 3 h with 3 replications were 22.91, 27.88 and 25.27 % respectively. The morphology of the particles by TEM showed that the nanoparticles were circular shape. Safety evaluation in mice resulted in the LD50 of NPL being greater than 5000 mg/kg in the acute toxicity study and had no adverse effects on blood, liver, and renal profiles in the subchronic toxicity study. The NPL-200 group had better effectiveness as an analgesic (84.87 %) compared to NPL-50 (37.80 %) and NPL-100 (69.15 %). This finding indicates that the NPL is a safe and effective formula for enhancing analgesic effects. Thus, enables its applications for the treatment of various diseases related to analgesics and inflammation such as osteoarthritis. HIGHLIGHTS The development of traditional medicine continues to be improved, to obtain the availability of safe, high quality, efficacious traditional medicines that are scientifically tested and can be widely utilized both for self-treatment by the community and in health services It is known that the most widely reported flavonoid derivative contained in edulis leaves is quercetin. Quercetin has poor bioavailability, solubility, and stability, reducing its therapeutic effect. By creating nanoparticles, adjustments can be made to natural products including quercetin in flavonoids in order to maximize their activity, boost their bioavailability, solubility, and capacity to be swiftly absorbed in the body to deliver the best possible therapeutic effects In developing nanoherbal passionfruit leaves using the ionic galation method, several solvents were used. It is known that no chemical substance can be said to be completely safe. It is important to study the toxicity profile further to obtain safe traditional medicines. Nanoparticle formulation of passion fruit leaf extract can provide better pain inhibition effectiveness in mice GRAPHICAL ABSTRACT

Non-clinical safety evaluation of Yongdamsagan-tang water extract: A 13-week subchronic oral toxicity study in Sprague Dawley rats.

Despite the continued clinical application of traditional herbal medicines, scientific evidence such as toxicological safety profile of Yongdamsagan-tang water extract (YSTW) has not yet been established. The purpose of this study was to investigate the potential toxicity profile of YSTW following a 13-week repeated oral administration at various concentrations to Sprague Dawley rats. YSTW was administered orally to rats once daily at doses of 0, 1000, 2000, and 5000 mg/kg bw/day for 13 weeks. During the experimental period, there were no significant toxicological changes related to YSTW treatment. These results indicate that the administration of YSTW for 13 weeks in the rat resulted in no signs of toxicity at up to 5000 mg/kg bw/day, which was considered the no-observed-adverse-effect level.

Protective Effect of Chlorogenic Acid Against Testicular Damage Induced By Glyphosate Isopropilamine in Rats

The aim of this subchronic toxicity study was to determine the prophylactic effect of chlorogenic acid (CGA) on the histopathologic-histologic changes and oxidative stress induced by Glyphosate isopropylamine (GLF-ISO) in testicular tissues. A sum of 42 male Wistar rats were divided into six equal groups, each containing 7 rats. For pretreatment, rats were given CGA at doses of 12.5, 25 and 50 mg/kg (po) and GLF-ISO at 787.85 mg/kg (po) for 7 weeks. GLF-ISO significantly increased malondialdehyde levels while decreasing SOD and CAT activities and GSH levels in testicular tissues. On the contrary, these parameters were improved in CGA-treated groups. Furthermore, CGA ameliorated the histopathological and histological changes in testicular tissues induced by GLF-ISO in a dose-dependent manner. The results indicate that testicular damage caused by GLF-ISO can potentially be prevented or managed by CGA.

Toxicological profile of Balanites agyptiaca in albino Wistar rats

Background: Balanites aegyptiaca (BAE) is a thorny tree that grows in most arid and semi-arid areas of Africa, the Middle East and India. It is used in traditional medicine for its cardioprotective, deworming, antihelmintic, anti-infectious and antifungal properties. Excessive consumption of this plant's products can present risks of intoxication for consumers. Objective: The aim of this study was to assess the acute and subchronic oral toxicity of the aqueous extract of Balanites aegyptiaca leaves and roots, with a view to ensuring the safety of consumers of this plant. Method: Acute toxicity was carried out in accordance with the OECD experimental protocol. The plant extract tested was administered orally to female rats at a single dose of 2000 mg/kg. These animals were observed for 14 days. For the subchronic toxicity study, the aqueous extract was administered daily orally to male and female rats at different doses (250, 500 and 1000 mg/kg) for 30 days. After the treatment period, the animals were sacrificed for hematological, biochemical and histopathological analyses. Results: The results of the acute oral toxicity test showed that the aqueous extract of Balanites aegyptiaca leaves and roots was non-toxic at a dose of 2000 mg/kg. During the sub-chronic test period, observation of rat signs and behaviour revealed no abnormalities in the groups of animals treated with the extract compared with controls. A significant variation in relative heart and liver weights was observed at 1000 mg/kg. In addition, there was a significant reduction in concentrations of aspartate aminotransferase, total cholesterol, triglycerides and low-density lipoproteins in these rats. Compared with control groups. There was also a significant decrease in hemoglobin and mean corpuscular hemoglobin, with an increase in lymphocytes and white blood cells at the same dose of 1000mg/kg. Histological examinations of the kidneys and liver showed normal renal architecture, and the liver also showed normal hepatic architecture with slight degeneration at a dose of 1000mg/kg of the extract tested. Conclusion: Single administration of the 2000 mg/kg dose did not induce signs of significant toxicity in rats. However, in long-term oral treatment, safety measures must be taken. Thus, sub-chronic oral exposure of BAE to lower doses is recommended, while higher doses, of the order of 1000 mg/kg, should be avoided.

Uncovering cocoa shell as a safe bioactive food ingredient: Nutritional and toxicological breakthroughs

This work aimed to analyze the chemical composition of the cocoa shell flour (CSF) and aqueous extract (CSE) and conduct acute and sub-chronic toxicity assays to ensure safety. CSF was composed of 59.1 % dietary fiber, primarily insoluble fiber (48.1 %). CSE consisted entirely of soluble fiber (72.8 %), mainly pectic polysaccharides. The amino acid profile revealed CSF's potential as a high-quality plant protein source, whereas CSE was rich in free amino acids, especially leucine, valine, and alanine (59.6–62.5 mg 100 g−1). Higher levels of macroelements, especially potassium, were found in CSE. Silicon was the most abundant microelement, and heavy metal levels were within acceptable limits for both cocoa shell matrices. This study confirmed the bioactive potential of CSF and CSE, enriched in phenolic compounds and methylxanthines, including theobromine, caffeine, gallic acid, (+)-catechin, as well as N-phenylpropenoyl-l-amino acids. The high theobromine content in both matrices, especially in CSE (2605.3 mg 100 g−1), did not harm the mice's health; acute and sub-chronic toxicity studies demonstrated the safety of oral administration of CSF and CSE in mice, showing no lethality or remarkable histopathological changes. This research supports the safe use of CSF and CSE, establishing these ingredients as suitable for incorporation into food products.

Acute and sub-chronic toxicity studies of methanol extract of Trema orientalis (Linn) blume in albino wistar rats

BackgroundThe safety potential of the methanol extract of Trema orientalis (TOM) leaf was evaluated in albino Wistar rats using biochemical, haematological, and histological indices in both acute and sub-chronic toxicity studies. MethodsThe animals were managed following the National Institute of Health (NIH) stipulated protocols for handling laboratory animals. The weight of each animal was recorded upon arrival and monitored throughout the study. The animals were allowed to acclimatize for 14 days, after which they were reweighed and randomly distributed into four groups of three female rats (n=12) for acute toxicity studies. Group A was given distilled water, and Groups B, C, and D were given a single dose of 2000, 4000, and 5000 mg/kg bw TOM extract, respectively. On day 15, each animal was anaesthetized and then euthanized. For the sub-chronic toxicity study, animals were randomly distributed into five groups of eight female rats (n=40). They were dosed daily for 28 days. Group A (Negative control group) was given distilled water. Groups B, C, and D had 200, 400, and 800 mg/kg bw TOM extract and Group E (Vehicle control group) were given 0.25 % of sodium carboxyl methyl cellulose (CMC). Five animals were anaesthetized and then euthanized on day 29, while three animals were kept for recovery evaluation for another two weeks without further administration of the extract. Ten organs were excised from each animal and weighed. The liver and kidney were processed for histopathological studies, while the blood samples were collected for biochemical and haematological assays. ResultsFrom acute toxicity studies, the LD50 value of TOM extract was estimated to exceed 5000 mg/kg bw via oral passage. From Sub-chronic toxicity studies, biochemical results showed a significant (p < 0.05) reduction in total protein, albumin, globulin, AST, ALP, and ALT in a dose-dependent manner. Histology of the liver and kidney tissues of all the animals except the kidney of the 800 mg/kg group had no visible lesions; this sets the safety dose for TOM at above 400 mg/kg but below 800 mg/kg. Recovery animals had significantly (p < 0.05) increased total protein, total bilirubin, and ALP and decreased albumin and direct bilirubin levels. ConclusionThis study reports the safety dose of TOM, a reputable medicinal plant extract. This is the first study reporting that the LD50 value of TOM extract exceeds 5000 mg/kg bw via oral passage.

The subchronic toxicity of higher olefins in Han Wistar rats

Higher olefins (HO) are a category of unsaturated hydrocarbons widely used in industry applications to make products essential for daily human life. Establishing safe exposure limits requires a solid data matrix that facilitates understanding of their toxicological profile. This in turn allows for data to be read across to other members of the category, which are structurally similar and have predictable physico-chemical properties. Five independent subchronic oral toxicity studies were conducted in Wistar rats with Oct-1-ene, Nonene, branched, Octadec-1-ene, Octadecene and hydrocarbon C12-30, olefin-rich, ethylene polymn. by product, at doses ranging from 20 to 1000 mg/kg bw. These HO were selected considering gut absorption, carbon chain length, double-bond position and carbon backbone structural variations. Generally, limited and non-adverse toxicity effects were observed at the end of the treatment for short carbon chain HO. For instance, alpha 2u-globulin nephropathy in the male rats and liver hypertrophy. No clear trend in systemic toxicity was linked to the double-bond position. Key factors for hazard assessment include absorption, carbon chain length, and branching, with Nonene, branched, identified as the worst-case substance. Taken together, the no observed adverse effect level (NOAEL) of each HO in these subchronic studies was set at the highest dose tested.

Subchronic inhalation toxicity study of diethylbenzene in Wistar rats

Subchronic inhalation toxicity study of diethylbenzene in Wistar rats

P16-02 Subchronic intramuscular toxicity and immunogenicity study of a plant-based SARS-CoV-2 vaccine in Sprague-Dawley rats with a 4-week recovery period

P16-02 Subchronic intramuscular toxicity and immunogenicity study of a plant-based SARS-CoV-2 vaccine in Sprague-Dawley rats with a 4-week recovery period

Safety evaluation of aqueous extract from Valeriana officinalis L. roots: Genotoxicity, acute, subchronic and teratology toxicity

Ethnopharmacological relevanceValeriana officinalis L., commonly known as “valerian”, is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. Aim of the studyThis study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). Materials and methodsThe genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague–Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague–Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. ResultsAEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. ConclusionIn vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.

Chemical profiling and quality evaluation of raw and vinegar-processing frankincense by multiple UPLC-MS/MS techniques.

Frankincense is used for analgesic, tumor-suppressive, and anti-inflammatory treatments in Traditional Chinese Medicine but poses toxicological concerns. Vinegar processing is a common technique used to reduce the toxicity of frankincense. This study aimed to investigate the chemical composition and quality evaluation of raw and vinegar-processing frankincense by multiple UPLC-MS/MS techniques. Additionally, we purposed refining the vinegar processing technique and identifying potentially harmful ingredients in the raw frankincense. Sub-chronic oral toxicity studies were conducted on raw and vinegar-processing frankincense in rats. The composition of frankincense was identified by UPLC-Q-TOF-MS/MS. Chemometrics were used to differentiate between raw and vinegar-processing frankincense. Potential chemical markers were identified by selecting differential components, which were further exactly determined by UPLC-QQQ-MS/MS. Moreover, the viability of the HepG2 cells of those components with reduced contents after vinegar processing was assessed. The toxicity of raw frankincense is attenuated by vinegar processing, among which vinegar-processing frankincense (R40) (herb weight: rice vinegar weight = 40:1) exhibited the lowest toxicity. A total of 83 components were identified from frankincense, including 40 triterpenoids, 37 diterpenoids, and 6 other types. The contents of six components decreased after vinegar-processing, with the lowest levels in R40. Three components, specifically 3α-acetoxy-11-keto-β-boswellic acid (AKBA), 3α-acetoxy-α-boswellic acid (α-ABA), and 3α-acetoxy-β-boswellic acid (β-ABA), inhibited the viability of HepG2 cells. The processing of frankincense with vinegar at a ratio of 40:1 could be an effective method of reducing the toxicity in raw frankincense. Our research improves understanding of the toxic substance basis and facilitates future assessments of frankincense quality.

Synthesis of glucosamine-selenium compound and evaluation of its oral toxicity and in vitro anti-hepatitis B virus activity

Selenium supplements are beneficial to human health, however, concerns regarding the toxicity of inorganic selenium have stimulated research on safer organic compounds. The main objective of this study was to develop a novel glucosamine-selenium compound (Se-GlcN), clarify its structure, and subsequently investigate its oral toxicity and in vitro anti-hepatitis B virus (HBV) activity. Electron microscopy, infrared, ultraviolet spectroscopy, nuclear magnetic resonance and thermogravimetric analyses revealed a unique binding mode of Se-GlcN, with the introduction of the Se-O bond at the C6 position, resulting in the formation of two carboxyl groups. In acute toxicity studies, the median lethal dose (LD50) of Se-GlcN in ICR mice was 92.31 mg/kg body weight (BW), with a 95 % confidence interval of 81.88–104.07 mg/kg BW. A 30-day subchronic toxicity study showed that 46.16 mg/kg BW Se-GlcN caused livers and kidneys damage in mice, whereas doses of 9.23 mg/kg BW and lower were safe for the livers and kidneys. In vitro studies, Se-GlcN at 1.25 μg/mL exhibited good anti-HBV activity, significantly reducing HBsAg, HBeAg, 3.5 kb HBV RNA and total HBV RNA by 45 %, 54 %, 84 %, 87 %, respectively. In conclusion, the Se-GlcN synthesized in this study provides potential possibilities and theoretical references for its use as an organic selenium supplement.

Toxicological evaluation of porcine bile powder in Kunming mice and Sprague-Dawley rats.

Background: Porcine bile powder (PBP) is a traditional Chinese medicine that has been used for centuries in various therapeutic applications. However, PBP has not previously undergone comprehensive component analysis and not been evaluated for safety through standard in vivo toxicological studies. Methods: In our study, we characterized the component of PBP by liquid chromatography-mass spectrometry. The acute and subchronic oral toxicity, genotoxicity, and teratogenicity studies of PBP were designed and conducted in Kunming mice and Sprague-Dawley (SD) rats. Results: The chemical analysis of PBP showed that the main components of PBP were bile acids (BAs), especially glycochenodeoxycholic acid. There were no signs of toxicity observed in the acute oral test and the subchronic test. In the genotoxicity tests, no positive results were observed in the bacterial reverse mutation test. Additionally, in the mammalian micronucleus test and mouse spermatocyte chromosomal aberration test, no abnormal chromosomes were observed. In the teratogenicity test, no abnormal fetal development was observed. Conclusion: Our findings demonstrate that PBP, composed mainly of BAs, is non-toxic and safe based on the conditions tested in this study.

Subchronic oral toxicity study of the synbiotic mulberry in male and female Wistar rats

Mulberry (Morus alba L) fruit is traditionally used in Chinese medicine and has several beneficial effects, such as hypoglycemic, hypolipidemic, and anti-oxidative effects. We previously developed the synbiotic mulberry (SM) containing probiotic Lactobacilli, prebiotic inulin, and mulberry powder. In food supplement development, toxicity is the most important criterion in food and drug regulations before commercialization. Thus, this study aimed to investigate the subchronic toxicity of SM in male and female Wistar rats to evaluate its biosafety. The subchronic toxicity study was conducted by daily oral administration of SM at doses of 250, 500, and 1000 mg/kgBW for 90 days. Male and female rats were evaluated for body weight, organ coefficients, biochemical and hematological parameters, and vital organ histology. The results showed no mortality or toxic changes in the subchronic toxicity study. These results suggested that no observed adverse effect level (NOAEL) of SM in male and female rats has been considered at 1000 mg/kgBW for subchronic toxicity study.

Safety assessment of enzymatically converted chicken bile as a novel food material: Genotoxicity, teratogenicity, and acute and subchronic toxicity studies.

Enzymatically converted chicken bile (CB), prepared by converting taurine deoxycholic acid (TCDCA) to taurine ursodeoxycholic acid (TUDCA) in CB, possesses various functional activities. But their nutrient composition and safety assessment have not been fully investigated yet. CB was mainly composed of proteins and steroids. CB did not show genotoxic effects based on Ames test, mammalian erythrocyte micronucleus test, and in vitro mammalian chromosomal aberration test. There were no growth abnormalities or deaths in the acute toxicity test for mice, indicating that CB is nontoxic with an LD50>10g/kg·body weight (BW). Subchronic toxicity test and genotoxicity test were performed based on intake of 0.5g CB per person daily at expanded doses of 33.3, 100, and 300 times (278, 833, and 2500mg/kg·BW). The result indicated that CB at 833mg/kg·BW showed no toxicity on BW, body weight gain, food intake, hematological, serum biochemistry, absolute/relative organ weights, urinalysis, and pathological features of rats in the subchronic toxicity test, while CB at 833mg/kg·BW induced maternal toxicity with no fetus teratogenicity or embryotoxicity in the teratogenicity test. In conclusion, CB did not show toxic effects and a long-term daily intake of CB at 0.5g per person is considered safe, but pregnant women should avoid it. These findings could provide a reference for the safe use of CB in functional food.

28-day repeated-dose toxicity of orally administered Jinmao Jiedu granule in Sprague-Dawley rats

Jinmao Jiedu granule is a Chinese medicine preparation consisting of Actinidia valvata Dunn, Salvia chinensis Benth, Iphigenia indica Kunth, and chicken gizzard. For many years, it has been employed in adjuvant therapy for cancer, especially liver cancer. However, the potential toxicity of the granule has not been reported. The present study aimed to assess the repeated-dose toxicity of orally administered Jinmao Jiedu granules for Sprague-Dawley (SD) rats. SD rats were orally administered Jinmao Jiedu granules at doses of 2.85, 5.70, and 11.40 g/kg in a 28-day subchronic toxicity study. No adverse clinical signs associated with treatment were noted throughout the experiment. There were no treatment-related toxicity alterations in body weight, hematology, clinical biochemistry, urinalysis, necropsy, and histopathology in rats compared with the control group. The No Observed Adverse Effect Level (NOAEL) of the Jinmao Jiedu granule was higher than 11.40 g/kg/day in rats.

A 90-day preclinical toxicological evaluation in rats of a highly purified and concentrated mulberry leaf extract.

Mulberry (genus Morus) leaves have long been used as a human food, especially in Asia, and animal feed. More recently, mulberry leaf extracts have been introduced as a convenient way to consume mulberry for non-nutritional functional effects. Reducose® 5% is an Morus alba leaf extract that has been highly purified and standardized to a content of 5 ± 0.5% 1-deoxynojirimycin, a naturally present polyhydroxylated piperidine alkaloid analog of D-glucose. This extract has previously been evaluated in acute and subacute (28-day) oral toxicity studies in which no adverse effects of the test item were observed in mice or rats, respectively. Due to continued and growing interest in the extract in multinational markets, we have now further investigated potential toxic effects in subchronic (90-day) oral toxicity study in male and female Han:WIST rats. The test item was administered at doses of 850, 1700, and 2550 mg/kg bw/day, and did not cause adverse effects in clinical signs, body weight development, clinical pathology, gross pathology, or histopathology in comparison to the vehicle-control group. The no-observed-adverse-effect-level was determined to be 2550 mg/kg bw/day. These results add to the existing body of both preclinical and clinical work relevant to the safety of the extract and of interest to regulators in various global markets.