JOURNAL OF FOOD SCIENCE
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2025
·Vol. 90
·期 3
·e70075
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IF 3.4
Xuefeng Qu,Qinxi Wang,Zemi Xie,Yuejin Wu,Yangjunna Zhang,Zhen Liu,Yin Wang
The Chlamydomonas reinhardtii (red) is a strain rich in protoporphyrin IX, which could be used as algal-derived novel sustainable nutritional sources. However, the safety research on C. reinhardtii (red) remains insufficient and further investigation is needed. In order to assess the safety of C. reinhardtii (red) and to expand its use in food applications, a series of toxicological safety evaluations were carried out to observe acute toxicity, subchronic toxicity and genotoxicity of C. reinhardtii (red). The C. reinhardtii (red) was administered to an acute oral toxicity test, mammalian micronucleus test, mouse chromosomal aberration test in Institute of Cancer Research (ICR) mice, and 90-day repeated-dose oral toxicity test in Sprague-Dawley (SD) rats. In the acute oral toxicological test, no mortality or abnormalities were observed in male and female rats, with an median lethal dose(Lethal Dose, 50%) (LD 50 ) exceeding 10.0 g/kg body weight (BW). Similarly, male and female mice exhibited no mortality or abnormalities, with an LD 50 surpassing 20.0 g/kg BW. The results of bacterial reverse mutation test, mammalian micronucleus test, and mouse chromosomal aberration test were all negative, suggesting that the C. reinhardtii (red) did not show mutagenicity under the conditions of this experiment. In a 90-day repeated-dose oral toxicity study, the SD rats were orally administered daily doses of 2.0 g/kg BW, 4.0 g/kg BW, and 8.0 g/kg BW without exhibiting any signs or symptoms of toxicity. Therefore, the no observed adverse effect level (NOAEL) of C. reinhardtii (red) was 8.0 g/kg BW/day. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food. Practical Application The aim of this study was to assess the safety of C. reinhardtii (red) and to expand its use in food applications. The major finding of this study is that the C. reinhardtii (red) did not show acute toxicity, subchronic toxicity and genotoxicity under the conditions of this experiment. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food.
研究领域:
毒理学
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食品安全
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营养学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2015
·Vol. 35
·期 11
·1415-1426
·
IF 2.982
Xu Wang,Ziqiang Tan,Yuanhu Pan,Awais Ihsan,Qianying Liu,Lingli Huang,Guyue Cheng,Dongmei Chen,Yanfei Tao,Zhenli Liu,Zonghui Yuan
Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD 50 calculated was 1400 mg kg –1 body weight (BW) day –1 in rats and 1130 mg kg –1 BW day –1 in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg –1 diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high-dose group. Treatment-related changes in clinical serum biochemistry were found in the medium- and high-dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg –1 diet, and significant decrease in relative weights of livers in males in the 100 mg kg –1 diet were noted. Histopathological observations revealed that the 1000 mg kg –1 ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no-observed-adverse-effect level for ADP was a 20 mg kg –1 diet, which is about 1.44-1.53 mg kg –1 BW day –1 in rats. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
药理学
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毒理学
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兽医学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
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2018
·
IF 2.518
Chun Lai LIANG,Qian XIANG,Wen Ming CUI,Jin FANG,Na Na SUN,Xiao Peng ZHANG,Yong Ning LI,Hui YANG,Zhou YU,Xu Dong JIA
Objective To investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes. Methods Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg·bw·day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined. Results There were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups. Conclusion Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.
研究领域:
毒理学
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纳米生物学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2024
·
IF 2.7
Guangzhen Zheng,Yong Zhu,Bingmin Wu,Xiaoyuan Xu,Juanjuan Cheng,Yan Liu,Song Huang,Jing Chen,Qingping Xiong,Jihang Chen
Resorcinol-formaldehyde aerogel (RFa) is a unique nanomaterial composed of polymer nanoparticles with a three-dimensional network structure. Our previous studies have demonstrated its application in the separation and purification of alkaloids, and we are exploring its application potential as the drug delivery carrier. Therefore, it is necessary to comprehensively understand the in vivo toxicity profile of RFa and evaluate its oral biosafety. In this work, we systematically evaluated the in vivo acute toxicity and subchronic oral toxicity of RFa in both male and female Kunming mice. During the 14-day acute toxicity test, the dose administered ( M = 580 mg/kg) was converted from the clinical dose of adsorbed alkaloids on RFa. The mice were gavaged only once and were observed continuously for 14 days. There were no abnormalities, and pathological changes in the major organs (heart, liver, spleen, lungs, kidneys, testes, and ovaries) were detected, followed by the 12-week subchronic toxicity test at the dose of 1/4 M , 1/2 M , and M . All mice were administered orally once daily and regularly observed throughout the experimental period. As a result, no abnormalities were found in body weights, food intake, and organ coefficients. Tissue section revealed no pathological changes in the major organs. In addition, there were no significant differences in hematological, blood biochemical, and coagulation parameters in both male and female mice compared to control group. These results showed that RFa was well tolerated at these dosage levels and did not cause significant toxic effects in Kunming mice. This study, as part of a broad research program on the biosafety of aerogel nanomaterials, provided the biosafety assurance for the subsequent study of RFa in biomedical applications.
研究领域:
毒理学
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纳米医学
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生物医药
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF TOXICOLOGY
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2023
·
IF 2.2
Xu Fang,Wei Zhu,Huiying Zhao,Wencheng Yin,Xiao Song,Fengxin Liu
Lacto-N-triose II (LNT II), an essential human milk oligosaccharide and precursor to lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), was evaluated for safety. Genotoxicity was assessed through in vitro tests including Bacterial Reverse Mutation Test and mammalian cell micronucleus test, and a subchronic oral gavage toxicity study was conducted on juvenile Sprague-Dawley rats. In this study, LNT II was administered at dose levels of 0, 1,500, 2,500, or 5,000 mg/kg body weight (bw)/day for 90 days, followed by a 4-week treatment-free recovery period. LNT II was non-genotoxic in the in vitro assays. No compound-related effects were observed across all dosage levels based on various measures, including clinical observations, body weight gain, feed consumption, clinical pathology, organ weights, and histopathology. Consequently, the highest dosage of 5,000 mg/kg bw/day was established as the no-observed-adverse-effect-level (NOAEL). These results suggest the safe use of LNT II in young children formula and as a food ingredient, within the limits found naturally in human breast milk.
研究领域:
营养学
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毒理学
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儿科学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2021
·
IF 4.219
Feng Li,Liping Wang,Yilei Cai,Yihuo Luo,Xianai Shi
In this work, the acute and subchronic toxicities of desaminotyrosine (DAT) by oral administration in SD rats and its effects on the intestinal microflora were investigated. The acute toxicity test showed that DAT is a low-toxic substance with a LD 50 of 3129 mg/kg. The subchronic toxicity test showed that DAT has no toxicity at a low dose (125 mg/kg/day). However, DAT exhibited obvious toxicities to food intake, liver, kidney, and lung at higher dose (250 mg/kg/day and 500 mg/kg/day). DAT inhibited the food intake of rats in a dose-dependent manner. Serum biochemical analysis showed that DAT can increase the serum glucose level of rats. Fecal microbiota analysis showed that DAT treatment can significantly change the intestinal microflora of rats, the dose of 125 mg/kg/day has the most significant effect on the diversity of intestinal microbiota. In daily application, the side effects caused by DAT might be gastrointestinal irritation , weight loss, liver or kidney injury , and blood sugar elevation. Based on our study, the no-observed-adverse-effect level (NOAEL) of DAT is 125 mg/kg BW/day for rats.
研究领域:
毒理学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2022
·
IF 10.753
Youai Zhang,Zhongkang Yang,Xianxu Li,Peipei Song,Jun Wang
Phthalate esters (PAEs) are widely used as plasticizers and can be ubiquitously detected in environment. However, the toxic effects and mechanisms of diisononyl phthalate (DINP) on earthworms are still poorly understood. In this study, earthworms ( Eisenia fetida ) were exposed to DINP at various doses (0, 300, 600, 1200, and 2400 mg/kg) to investigate their subchronic toxicity. The results demonstrated that the reactive oxygen species (ROS) levels displayed an “increase-decrease” trend with the increasing DINP doses after DINP exposure on days 7, 14, 21, and 28. The malondialdehyde (MDA) content increased with increasing DINP doses on days 7, 14, and then decreased on days 21, 28. The values of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) showed similar variation patterns and reached a maximum level on 21 d. Moreover, on day 28, the SOD and CAT gene expression levels were upregulated, while the GST gene expression levels were downregulated. Meanwhile, 16S rRNA genes of E. fetida gut bacteria and surrounding soil bacteria were measured after 28 days of exposure to DINP. The Chao index of E. fetida gut bacteria decreased when the treatment with the highest concentration (2400 mg/kg) was applied. At the phylum level, the abundance of Chloroflexi was significantly lower in the gut of E. fetida . In addition, the abundance of Proteobacteria at the phylum level and Ottowia at the genus level significantly increased in the surrounding soil. Overall, our results shed light on the toxic mechanism of DINP at biochemical, molecular, and omics levels, and contributed to a better understanding of the ecotoxicity of DINP.
研究领域:
环境科学
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毒理学
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微生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Wu Lirong,Wang Jieyi,Lei Jing,Ge Kun,Qu Chun,Liu Jiajian,Huang Fengjie,Sun Dongnan,Chao Xiaowen,Chen Tianlu,Zhao Aihua,Jia Wei,Zheng Xiaojiao,Xie Guoxiang
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.
研究领域:
药理学
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毒理学
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传统中药
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产品关联
DOI
PubMed
高影响因子
REGULATORY TOXICOLOGY AND PHARMACOLOGY
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2023
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IF 3.4
Lang Yan,Jingjing Mao,Wenjing Shi,Lijun Ren,Jinfeng Li,Bijiang Geng,Haoneng Wang,Jiqianzhu Zhang,Yijun Tian,Bin Zhang,Fangyuan Gao,Xiaofang Zhang,Jikuai Chen,Jiangbo Zhu
In this study, the toxicity of ferric oxide nanoparticles (Fe 2 O 3 NPs) administered through gavage to Sprague Dawley (SD) rats for 94 d, consecutively and the recovery after Fe 2 O 3 NPs withdrawal for 30 d were evaluated. The vehicle control group, low-, medium-, and high-dose groups were administered with the vehicle (0.5% sodium carboxymethyl cellulose [CMC-Na]), 125, 250, and 500 mg/kg of Fe 2 O 3 NPs, respectively, administered every morning for 94 d. There was no significant difference in the body weight, food intake, hematological, blood biochemical, and urine indices of SD rats in each administration group and the control group (P > 0.05). There was no significant difference in organ weight, organ indices, and the coefficient of the visceral brain between the SD rats in the different dosage groups and the SD rats in the vehicle control group (P > 0.05). Histopathological observations showed that there was no correlation between the pathological lesions of the organs observed in this study and the dose of Fe 2 O 3 NPs (P > 0.05). The no-observed-adverse-effect level (NOAEL) dose of Fe 2 O 3 NPs was initially determined to be 500 mg/kg administered to SD rats through oral gavage for 94 d, consecutively, followed by recovery after Fe 2 O 3 NPs withdrawal for 30 d.
研究领域:
毒理学
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纳米医学
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实验动物学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2025
·
IF 4.3
Liu-Yan Liang,Ting-Yin Lu,Long-Gen Zhong,Wen-Hui Su,Zi-Qi Ren,Meng-Ting Tao,Jian Sun,Xiao-Ping Liao,Dong-Hao Zhao,Yu-Feng Zhou
Shikimic acid, a widely known hydroaromatic compound abundantly found in Illicium verum (commonly known as Chinese star anise), serves as a key intermediate in the synthesis of neuraminidase inhibitors such as oseltamivir. However, its pharmacokinetic (PK) properties and long-term safety profile remain inadequately characterized. This study systematically evaluated its PK behavior following both oral and intravenous administrations, along with its acute toxicity and 28-day subchronic oral toxicity in mice. PK analysis for shikimic acid demonstrated linear and dose-proportional behavior within the intravenous dose range of 4–16 mg/kg. Shikimic acid was rapidly eliminated from plasma, with a short terminal half-life (T1/2) of 0.76–0.85 h. Despite rapid absorption (Tmax, 0.95–1.25 h) following oral administration, a low bioavailability ranging from 11.09 to 20.44% was observed in mice. Acute toxicity testing showed no mortality at oral doses of up to 10,000 mg/kg. In the 28-day subchronic oral toxicity study, mice fed diets containing high (50 g/kg), medium (16.67 g/kg), or low (5.56 g/kg) doses of shikimic acid exhibited no mortality. Hematological assessments revealed slight elevations in neutrophil counts, eosinophil counts, and hematocrit levels in the high-dose group compared to controls. Notably, a significant reduction in triglyceride levels was observed in the high-dose group, suggesting potential hypolipidemic effects for shikimic acid. Collectively, these findings provide foundational data on the PKs, safety, and tolerability of shikimic acid, supporting its further development for potential therapeutic applications.
研究领域:
药理学
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毒理学
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药物代谢
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生物药剂学
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药物化学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Hong Ding,Xuanxiao Lu,Xiaoguo Ji,Shijie Wang,Jiayang Jin,Mengyao Zhao,Xiaofeng Hang,Liming Zhao
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 (LD 50 ) of Se-GlcN in ICR mice was 92.31 mg/kg body weight (BW), with a 95% confidence interval of 81.88 to 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.
研究领域:
药物化学
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毒理学
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病毒学
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药理学
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产品关联
DOI
PubMed
高影响因子
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