Despite increasing reports of using silica nanoparticles (SNPs) for controlled drug delivery applications, their long-term toxicity profile following intravenous administration remains unexplored. ...Herein, we investigated the acute (10-day) and subchronic (60-day and 180-day) toxicity of nonporous SNPs of approximately 50 nm (Stöber SNPs50) and approximately 500 nm in diameter (Stöber SNPs500), and mesoporous SNPs of approximately 500 nm in diameter (MSNPs500) upon single-dose intravenous injection into male and female immune-competent inbred BALB/c mice. The Maximum Tolerated Dose (MTD) of the particles was determined 10 days post-injection. The MTD of SNPs was administered and toxicity evaluated over 60 and 180 days. Results demonstrate that Stöber SNPs50 exhibit systemic toxicity with MTD of 103 ± 11 mg.kg−1 for female and 100 ± 6 mg.kg−1 for male mice, respectively. Toxicity was alleviated by increasing the size of the particles (Stöber SNPs500). MTD values of 303 ± 4 mg.kg−1 for female and 300 ± 13 mg.kg−1 for male were observed for Stöber SNPs500. Mesoporous SNPs500 showed considerable systemic sex-related toxicity, with MTDs ranging from 40 ± 2 mg.kg−1 to 95 ± 2 mg.kg−1 for male and female mice, respectively. Studies of SNPs showed blood toxicity as a function of physiochemical properties such as significant differences in the mean corpuscular hemoglobin (MCHC) and platelet number at day 10 and white blood cell count at day 60. Histological examination also showed size-, porosity- and time-dependent tissue toxicity. Stöber SNPs500 caused major toxic effects such as lung thrombosis, cardiac wall fibrosis and calcifications, brain infarctions with necrotizing inflammatory response, infiltrate, retinal injuries with calcification and focal gliosis, renal parenchymal damage and liver lobular inflammation dependent on the dose and time of exposure. However, tissue toxicity and accumulation of SNPs in liver observed at day 10 was greater than at day 60 and much greater than at day 180. In contrast, a dramatic increase in cytokine levels was observed at day 60. Despite the relatively high doses, SNPs did not cause subchronic toxicity at day 180 after single-dose intravenous injection. However, they showed distinct differences in the 60 day in vivo subchronic toxicity and inflammation profile as a function of surface area and size.
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As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a ...90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.
•The dietary exposure assessment of GMC in China was conducted.•No significant toxicity was detected after 90 days of GMC exposure.•The current dietary exposure of GMC in China is safe for consumers.
The study was planned to evaluate toxicity of M. oleifera leaf methanol extract in Wistar rats, cytotoxic potential and chemically characterize it. Acute toxicity study revealed no mortality at ...2,000 mg/kg dose. In subchronic toxicity, 150, 300, and 600 mg/kg extract were administered in both sexes for 90 days. A decrease in body weight, cholesterol, and low‐density lipoproteins, as well as an increase in the platelet count were observed. The histology of heart, lung, and kidney was normal. The oxidative stress biomarkers were normal in the liver tissue. In vitro cytotoxicity assay revealed that IC50 of the plant extract was more than 1,000 µg/ml. FTIR explored various functional groups and HPLC analysis indicated the presence of kaempferol and quercetin in the plant extract. These results showed that the plant extract might be safe up to 2,000 mg/kg single dose. The long term use of the plant extract was mostly devoid of major system toxicities.
Practical applications
M. oleifera is a multipurpose tree. It is a cruciferous plant that has nutritional as well as medicinal properties. It is exhibited a multitude of nutraceutical or pharmacological properties such as anti‐inflammatory, lipid‐lowering, anticancer, hypoglycemic, and antihypertensive activities. It is widely used by local inhabitants for their health, food, agriculture, and cosmetic purposes. Among other plant parts, its leaves are mostly used as a functional food because of abundant proteins, β‐carotene, polyphenol, vitamin C, and vitamin E. The current study was designed to validate its safety in acute and long term use. The data of this study suggested that the plant can be safely used as a nutraceutical as well as a nutritional food.
The FTIR explored various functional groups and HPLC analysis indicated the presence of kaempferol and quercetin in the methanol extract of Moringa oleifera leaf.
In vitro cytotoxicity assay revealed that IC50 of the plant extract was more than 1,000 µg/ml.
The plant extract might be safe up to 2,000 mg/kg single dose. Long term use of the plant extract was mostly devoid of major system toxicities.
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.
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•SM containing probiotic Lactobacilli, prebiotic inulin, and mulberry powder.•No correlation between the organ coefficient and SM.•NOAEL of SM in both male and female rats was 1000 mg/kg BW.
Propyl-propane-thiosulfonate (PTSO) is one of the main organosulfur compounds present in Allium essentials oil. Different applications in the food sector have been proposed for PTSO, such as food and ...feed additive and as active packaging. However, the authorization of its use depends on its toxicity profile. Thus, as a part of its safety assessment, in this work a repeated dose 90-day oral toxicity study has been conducted for the first time in rats following the OECD guideline 408. PTSO was administered to groups of 10 male and 10 female rats at dose levels of 0, 14, 28, and 55 mg/kg/day. No clinical signs or mortality and no changes in body weight, food consumption and feed conversion efficiency were detected through the study. Moreover, no treatment-related changes in hematological and biochemical parameters were observed, for either sex or dose groups. The histopathology study performed revealed no differences in organ weights, and no morphological and histopathological changes were observed. Based on these results, the no-observed-adverse-effect level (NOAEL) of PTSO was judged to be ≥ 55 mg/kg/day for both sexes.
•A 90 days oral toxicity study was conducted with propyl-propane-thiosulfonate.•PTSO did not induce toxic effects at the highest dose assayed (55 mg/kg/day).•NOAEL for PTSO was estimated to be ≥ 55 mg/kg/day.
Monascus Color Y-001, a natural food pigment produced from Monascus purpureus Y-001 fermentation, was administered orally by gavage to 4 Beagle dogs/sex/group for 90 days at doses of 0 (vehicle: 0.1% ...Tween 80, 10 mL/kg bw), 1, 5 and 25 mg/kg bw/day. In the clinical observations, vomiting/vomitus (dark red watery substance or undigested feed) was observed for males and females in the 25, but not 5 or 1 mg/kg bw/day group at a relatively high frequency. In addition, loose stools were observed for males in this group on a single occasion. These signs were considered to be effects of the test article on the digestive tract. No treatment-related effects were noted in the detailed observations for symptoms, body weights, food consumptions, ophthalmology, hematology, clinical chemistry, urinalysis, gross pathology, organ weights or histopathology. Thus, the no-observed-adverse-effect level (NOAEL) was judged to be 5 mg/kg bw/day in both sexes of the dogs.
Subtilisin NAT, a Bacillus subtilisin, is widely applied as a functional food and considered to be one of the most exploitable potential oral thrombolytic agents. Subtilisin QK, another Bacillus ...subtilisin, is a serine protease fermented by Bacillus subtilis 02 and has a better thrombolytic effect. Therefore, subtilisin QK is typically used for evaluating the safety of Bacillus subtilisins. Here, we conduct several good laboratory practice (GLP)-compliant studies in non-rodent animal, i.e. in Beagle dogs, including acute toxicity, subchronic toxicity, and safety pharmacology studies. No adverse effects were evident in the acute and 28-day subchronic toxicity studies at doses up to 40000 FU/kg and 16000 FU/kg/day, respectively. In evaluating the pharmacological safety of up to 2000FU/kg subtilisin QK, we found no significant differences between the electrocardiograms, blood pressures, and respiration of beagle dogs. These findings suggest the safety of Bacillus subtilisin, providing reliable pharmacological and toxicological data for its development and popularization as a functional food and drug.
Lithocarpus litseifolius although known as “Sweet Tea” (ST), has been traditionally accepted as a daily beverage and used as a folk medicine in southern China with little understanding of its ...potential toxicity. This study evaluated the safety of a water extract of ST by a subchronic toxicity study in Sprague-Dawley rats. A total of 80 rats were randomized divided into 4 groups with 10 males and 10 females in each group, treated with 2000, 1,000, 500 and 0 mg/kg body weight of ST extract by gavage for 90 days, respectively. The results of the study showed that ST extract did not induce treatment-related changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine indices, and histopathology in rats. The NOAEL of ST extract was observed to be 2000 mg/kg/day for rats of both sexes. These results indicated that ST extract was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.
Xylitol is a hygroscopic compound known to protect nasal cavity against bacteria. It has also been developed into nasal spray and evaluated as a potential candidate drug for respiratory diseases. ...Consequently, it is necessary to study its inhalation toxicity. Based on our previous study on its subacute inhalation toxicity, this study aimed to investigate the safety of xylitol inhalation for long-term use. According to the OECD Test Guideline 413, Sprague-Dawley rats were randomly divided into six groups and exposed with different concentrations of xylitol aerosol or air. After exposure for 90-day, the recovery groups were continued to observe for a recovery period of 28-day. No significant changes in body weight were observed between sham and xylitol groups. Several significant differences in hematological, clinical chemistry, bronchoalveolar lavage fluid were observed, which either had no dose-effect relationship for both male and female rats or were restored during the recovery period. Finally, except for high dose group of xylitol, two rats showed a small amount of inflammatory exudate in alveolar and bronchial cavities, which was restored in the recovery period. The rest of rats showed no obvious difference. For the recovery groups, no significant difference was observed between these two groups. In conclusion, the no observable adverse effect level (NOAEL) of xylitol in our subchronic inhalation toxicological experiments was 2.9 mg/L, which indicated that xylitol for rats' long-time inhalation is tolerant and safe.
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•Subchronic inhalation toxicity of xylitol was assessed in rats exposed for 90 days.•The NOAEL of xylitol in subchronic inhalation toxicology is 2.9 mg/L.•Xylitol for long-time inhalation is tolerant and safety for rats.
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