JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 3
·e70075
·
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
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Hailin Long,Xuehong Qiu,Li Cao,Guiqing Liu,Zhongchen Rao,Richou Han
Ethnopharmacological relevance The Chinese cordyceps, a parasitic Thitarodes insect- Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, is one of the most valuable traditional Chinese medicines and health food for ameliorating conditions associated with aging and for treating fatigue, night sweats, hyperglycemia, hyperlipidemia, respiratory, renal and liver diseases, and hyposexuality. The natural Chinese cordyceps resource is rare due to its harsh growing environment, limited geographical distribution and global climate warming. Artificial cultivation of Chinese cordyceps has been successfully established to meet its high demand in market. Aims of the study The present study aims to evaluate the toxicological safety of the cultivated Chinese cordyceps and provide scientific data for subsequent development and utilization of this valuable biological resource. Materials and methods The Chinese cordyceps was cultivated by mimicking the habitat environment in low-altitude areas and identified by morphological and microscopic characteristics. Its phytochemical profile was determined by the HPLC. Toxicological studies based on the cultivated Chinese cordyceps were conducted, including chromosomal aberration test of Chinese hamster lung (CHL) cells, Ames test, acute toxicity test and micronucleus (MN) test of bone marrow cells. Results The Chinese cordyceps successfully cultivated in low-altitude areas exhibited the same morphological and microscopic characteristics as natural Chinese cordyceps. The adenosine content was in accordance with the Chinese Pharmacopoeia (2015 Edition). The HPLC fingerprint was determined and five main chromatographic peaks representing uracil, uridine, inosine, guanosine and adenosine were identified. No dose-dependent increase in the rates of chromosomal aberration was detected in the presence or absence of metabolic activation system. Ames test also demonstrated no dose-dependent increase in the number of reversion mutation for five bacterial strains, with or without rat liver microsomal enzyme mixture (S9) metabolic activation, at a quantity range of 128–5000 μg cultivated Chinese cordyceps per plate. The acute toxicity test with mice showed that after 20 g/kg oral administration of cultivated Chinese cordyceps, neither animal death nor any abnormal change in general dissection of various tissues and organs of the animals were found within 14 days. The median lethal dose (LD 50 ) was greater than 5 g/kg, which is regarded as a non-toxic level, and maximum tolerable dose (MTD) of cultivated Chinese cordyceps in ICR mice was more than 20 g/kg. MN test of mouse bone marrow cells indicated no significant differences among each sample dose and the negative control. Conclusion Based on the results from four toxicological tests, it was concluded that the cultivated Chinese cordyceps was classified as non-toxic in one single administration at high doses by intragastric route in mice. This study provides scientific experimental basis for its safety.
研究领域:
药理学
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毒理学
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传统中药研究
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2025
·
IF 7.7
Yuanzhao Wu,Fengjun Fan,Lu Zhou,Yihang Shen,Anli Wang,Yazhou Qin,Jiye Wang,Weixuan Yao
As an emerging pollutant, the synthetic cannabinoid N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is widely abused and frequently detected in metropolitan wastewater. However, its effect on aquatic organisms remains unexplored. In this study, embryonic and larval zebrafish were exposed to sublethal concentrations of ADB-FUBINACA to assess its toxic effects via behavioral, biochemical, and metabolomic analyses. The observed morphological defects included reduced heartbeat, shorter body length, spinal deformation, and pericardial edema. Transgenic zebrafish exhibited cardiac developmental defects and apoptosis, indicating that cardiotoxicity is associated with dysregulated gene expression. Impaired motor activity and disrupted neuronal development suggested neurotoxicity. Elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels indicate oxidative stress, whereas transcriptional changes in immune-related genes reflect a dysregulated inflammatory response. Metabolomic analyses revealed disruptions in pathways related to alanine, purine, and pyrimidine metabolism, and arginine biosynthesis, which correlated with oxidative damage, cardiotoxicity, and neurodevelopmental effects. In conclusion, ADB-FUBINACA induces developmental toxicity in zebrafish embryos via oxidative stress and metabolic disruption, highlighting the potential environmental risks posed by this emerging pollutant.
研究领域:
环境科学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Yuanzhao Wu,Tianyi Chen,Yumei Xia,Jiawen Wang,Anli Wang,Binjie Wang,Jiye Wang,Weixuan Yao
Methidathion is a highly effective organophosphorus pesticide and is extensively utilized for the control of insects in agricultural production. However, there is little information on the adverse effects and underlying mechanisms of methidathion on aquatic organisms . In this work, embryonic zebrafish were exposed to methidathion at concentrations of 4, 10, and 25 mg/L for 96 h, and morphological changes and activities of antioxidant indicators alterations were detected. In addition, the locomotor behavioral abilities of zebrafish exposed to methidathion were also measured. To further explore the mechanism of the toxic effects of methidathion, gene expression levels associated with cardiac development, cell apoptosis, and the immune system were tested through qPCR assays. The findings revealed that methidathion exposure could induce a decrease in survival rate, hatchability, length of body, and increase in abnormality of zebrafish, as well as cardiac developmental toxicity . The LC 50 value of methidathion in zebrafish embryos was determined to be about 30.72 mg/L at 96 hpf. Additionally, methidathion exposure triggered oxidative stress in zebrafish by increasing SOD activity, ROS, and MDA content. Acridine orange (AO) staining indicated that methidathion exposure led to apoptosis, which was mainly distributed in the pericardial region. Furthermore, significant impairments of locomotor activity in zebrafish larvae were induced by methidathion exposure. Lastly, the expression of pro-inflammatory factors including IFN-γ, IL-6, IL-8, CXCL-clc, TLR4 , and MYD88 significantly up-regulated in exposed zebrafish. Taken together, the results in this work illustrated that methidathion caused developmental toxicity, cardiotoxicity, and immunotoxicity in embryogenetic zebrafish.
研究领域:
环境科学
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毒理学
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水生生物学
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产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2024
·Vol. 11
·期 5
·1817-1846
·
IF 5.8
Yiqun Mo,Yue Zhang,Qunwei Zhang
With the exponential growth of the nanotechnology field, the global nanotechnology market is on an upward track with fast-growing jobs. Nickel (Ni)-containing nanoparticles (NPs), an important class of transition metal nanoparticles, have been extensively used in industrial and biomedical fields due to their unique nanostructural, physical, and chemical properties. Millions of people have been/are going to be exposed to Ni-containing NPs in occupational and non-occupational settings. Therefore, there are increasing concerns over the hazardous effects of Ni-containing NPs on health and the environment. The respiratory tract is a major portal of entry for Ni-containing NPs; thus, the adverse effects of Ni-containing NPs on the respiratory system, especially the lungs, have been a focus of scientific study. This review summarized previous studies, published before December 1, 2023, on the cytotoxic, genotoxic, and carcinogenic effects of Ni-containing NPs on humans, lung cells in vitro, and rodent lungs in vivo, and the potential underlying mechanisms were also included. In addition, whether these adverse effects were induced by NPs themselves or Ni ions released from the NPs was also discussed. The extra-pulmonary effects of Ni-containing NPs were briefly mentioned. This review will provide us with a comprehensive view of the pulmonary effects of Ni-containing NPs and their underlying mechanisms, which will shed light on our future studies, including the urgency and necessity to produce engineered Ni-containing NPs with controlled and reduced toxicity, and also provide a scientific basis for developing nanoparticle exposure limits and policies.
研究领域:
毒理学
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环境健康
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Qi Han,Wenyi Dong,Hongjie Wang,Hang Ma,Peng Liu,Yurong Gu,Hongkai Fan,Xin Song
This study systematically investigated the performance of ozonation on tetrabromobisphenol A (TBBPA) degradation under different ozone dosages (5.21–83.33 μmoL/L), initial solution pH (3.0–11.0) and temperatures (10–50 °C). At the same time, the generations of inorganic products (bromide ion and bromate) under different experimental conditions were evaluated and the organic products were also identified. Then, the possible mechanism was proposed and verified by the quantum chemical calculation. In addition, variations and controlling of the toxicity were also analyzed, including acute toxicity, chronic toxicity and genotoxicity. Ozonation was proved to be an efficient and promising technology for removing TBBPA from water. TBBPA of 1.84 μmoL/L could be completely degraded within 5 min under the ozone dosage of 41.67 μmoL/L in wide ranges of pH (3.0–11.0) and temperature (10–40 °C). During the degradation of TBBPA, over 65% of the average bromine ion was detected and nine products were identified. The proposed degradation pathways verified that TBBPA might undergo addition and stepwise oxidative debromination, the hydrogen extraction, and the deprotonation. The results of toxicity testing showed that ozonation could effectively control the acute and chronic toxicity of the water samples, although the toxicity increased in the initial reaction stage due to the accumulation of more toxic intermediates.
研究领域:
环境科学
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化学工程
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2017
·
IF 1.74
Feng Li,Yijia Li,Qingxian Li,Xianai Shi,Yanghao Guo
The interest focusing on Eriobotrya japonica leaf triterpene acid (ELTA) has increased recently because of its beneficial effects on health. However, there has been a lack of experimental data on its toxicity. The present study therefore was conducted to evaluate its toxicity in ICR mice. The results showed that ELTA produced neither mortality nor toxicity of the main organs in ICR male and female mice in both acute (0.30, 0.65, 1.39, and 3.00 g·kg−1 body weight) and subacute (150, 300, and 600 mg·kg−1 BW) 28-day toxicity studies. Because of lacking apparently adverse effects found in the hematology, clinical biochemistry, and histopathology evaluation, results of the present study together with the beneficial effects make ELTA as a promising dietary supplement and indicated that ELTA administered orally might have a large safety margin for human.
研究领域:
药理学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
REGULATORY TOXICOLOGY AND PHARMACOLOGY
·
2015
·
IF 2.031
Xin Wu,Dan Wan,Chunyan Xie,Tiejun Li,Ruilin Huang,Xugang Shu,Zheng Ruan,Zeyuan Deng,Yulong Yin
N -carbamylglutamate (NCG) is a metabolically stable analog of N -acetylglutamate that activates carbamyl phosphate synthase-1, a key arginine synthesis enzyme in enterocytes. It is a promising feed additive in swine in China. In this study, we assessed the acute and sub-acute toxicity of NCG in Sprague–Dawley (SD) rats. All rats survived until they were killed at a scheduled time point. No adverse effects or mortality was observed following acute oral administration of 5000 mg/kg NCG to SD rats. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, a functional observational battery, organ weights, histopathology , ophthalmology, hematology, coagulation, and clinical chemistry parameters in any of the treatment groups in sub-acute doses of NCG at target concentrations corresponding to 500, 2000, and 3000 mg/kg/day for 28 days neither. In addition, no evidence of mutagenicity or genotoxicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that NCG is a non-toxic substance with no genotoxicity.
研究领域:
毒理学
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动物营养学
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分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Juan Wang,Xiangsheng Hong,Wang Liu,Le Zhang,Saihong Yan,Zhitong Li,Jinmiao Zha
As substitutes for bisphenol A (BPA), bisphenol analogs (BPs) have raised concerns due to their frequent environmental detection and unclear safety. Here, the cytotoxicity, endocrine disruption, neurotoxicity, aryl hydrocarbon receptor (AhR) activity, and genotoxicity of nine BPs and BPA were evaluated in three types of cell lines. Over half of the tested BPs exhibited greater cytotoxicity than BPA, with IC50 values showing a linear correlation with Log Kow (R²=0.69). All tested BPs exhibited at least one endocrine-disrupting effect, notably estrogenic, which was observable even at 0.01–0.1 μM. Importantly, BPAF and BPAP exposure had widespread endocrine-suppressing effects. Moreover, all BPs (except BPP) and BPA increased SH-SY5Y cells apoptosis at 1–10 μM. Only BPF and BPP significantly increased 7-ethoxyresorufin-O-deethylase levels, highlighting their notable effects on AhR activity. BPAF significantly induced DNA damage at 1.25 μM, whereas BPA, BPF, and BPP induced damage at 20, 25, and 25 μM, respectively. Finally, ToxPi, a weighted scoring system, was used to rank the comprehensive toxicity of BPs, with 7 of 9 BPs showing higher scores than BPA. Collectively, BPs generally exhibited stronger comprehensive toxicity compared with BPA, emphasizing the urgent need for further research to confirm their potential health implications.
研究领域:
毒理学
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环境科学
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生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Water
·
2022
·Vol. 14
·期 16
·2543
·
IF 3.53
Qi Han,Wenyi Dong,Hongjie Wang,Boping Yu,Peng Liu,Linshen Xie,Zhiguang Dai
This study has focused on the evaluation of the biotoxicity controlling effects during the TBBPA degradation by ozonation, including the acute, chronic and genetic toxicity under different [O3]/[TBBPA] (1:1–11:1), initial solution pH (5.0–9.0) and temperatures (10–40 °C). In addition, the comprehensive biotoxicity of the treated water sample was evaluated by the method of potential ecotoxic effects probe (PEEP). The results showed that TBBPA could be completely degraded with an initial solution pH of 7.0, temperature of 25 °C and an [O3]/[TBBPA] ratio of 9:1. The chronic toxicity of the untreated sample was as high as 41.7 TU, which represented the main toxicity of TBBPA itself. In contrast, the TBBPA showed a much lower acute and genetic toxicity in this study. During the process of TBBPA degradation, the ozonation could effectively control the toxicity of wastewater and showed strong adaptability. When the ratio of [O3]/[TBBPA] was 11:1, the acute and chronic toxicity were reduced to 0.02 TU and 0.76 TU, respectively, with the controlling rates being as high as 96% and 98.2% and meeting the emission standards. The mutagenicity ratio of the water sample was less than 2.0, indicating no genotoxicity risk. The evaluation of the comprehensive biological toxicity showed that ozonation could control the PEEP value below 2.0 in ranges of low [O3]/[TBBPA] ratio (3:1), wide pH (5–9) and temperatures (10–40 °C).Keywords:ozonation;tetrabromobisphenol A;acute toxicity;chronic toxicity;comprehensive biological toxicity
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2017
·
IF 3.778
Xiayun Yang,Shusheng Tang,Chongshan Dai,Daowen Li,Shen Zhang,Sijun Deng,Yan Zhou,Xilong Xiao
Quinocetone (QCT) has been used as an animal feed additive in China since 2003. However, investigations indicate that QCT has potential toxicity due to the fact that it shows cytotoxicity, genotoxicity , hepatotoxicity, nephrotoxicity and immunotoxicity in vitro and animal models. Although QCT-induced mitochondrial apoptosis has been established, the molecular mechanism remains unclear. This study was aimed to investigate the role of voltage-dependent anion channel 1 (VDAC1) oligomerization and Wnt/β-catenin pathway in QCT-induced mitochondrial apoptosis. The results showed VDAC inhibitor 4, 4-diisothiocyano stilbene-2, 2-disulfonic acid (DIDS) partly compromised QCT-induced cell viability decrease (from 34.1% to 68.5%) and mitochondrial apoptosis accompanied by abating VDAC1 oligomerization, cytochrome c (Cyt c ) release and the expression levels of cleaved caspase-9, -3 and poly (ADP-ribose) polymerase (PARP). Meanwhile, overexpression VDAC1 exacerbated QCT-induced VDAC1 oligomerization and Cyt c release. In addition, lithium chloride (LiCl), an activator of Wnt/β-catenin pathway, markedly attenuated QCT-induced mitochondrial apoptosis by partly restoring the expression levels of Wnt1 and β-catenin. Finally, reactive oxygen species (ROS) scavenger N -acetyl- l -cysteine (NAC) obviously blocked QCT-induced VDAC1 oligomerization and the inhibition of Wnt1/β-catenin pathway. Taken together, our results reveal that QCT induces mitochondrial apoptosis by ROS-dependent promotion of VDAC1 oligomerization and suppression of Wnt1/β-catenin pathway.
研究领域:
毒理学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Wang Junqi,Jing Xian,Hua Lizhong,Zheng Yuling,Hu Shiheng,Xiao Jing,Guo Dawei,Wu Wenda,Ji Hui,Peng Lin,Jiang Shanxiang,Gao Xiuge
Chloroquine was once thought to be a promising treatment for COVID-19 but it quickly failed due to its inefficiency and association with increased mortality. Further, comorbidities such as hypertension may have contributed this failure. The safety and toxicity of chloroquine at doses required for treating SARS-CoV-2 infection in hypertensive patients remain unknown. Herein, to investigate these effects, we performed a safety evaluation of chloroquine at the approved dose (63 mg/kg) and at a high dose (126 mg/kg) in hypertensive rats. We found that chloroquine increased the mortality of hypertensive rats to 18.2% and 100%, respectively, after 7 days. During the chloroquine exposure period, the bodyweight, feed, and water consumption of hypertensive rats were decreased significantly. In addition, we show that chloroquine induces prolongation of QTc interval, elevation of LDH and CK, and histopathological damage of the myocardium in hypertensive rats. Ocular toxicity was observed in hypertensive rats in the form of hemorrhage in the eyes and retinal damage. Furthermore, we also observed intestinal toxicity in hypertensive rats, which presented as thinning intestinal walls with hemorrhagic contents, and histopathological changes of the jejunum. Hepatotoxicity was also evidenced by elevated ALT, and vacuolization of hepatocytes was also observed. Nephrotoxicity was observed only in high dose chloroquine-treated hypertensive rats, presenting as alterations of urinalysis and renal function. Immune alterations were also found in high-dose chloroquine-treated hypertensive rats with elevation of serum IL-10, IL-1β and GRO, and moderate damage to the spleen. In summary, this study partially explains the reason for the failure of chloroquine as a COVID-19 therapy, and underlines the importance of safety evaluation and medical supervision of chloroquine to avoid patient harm, especially to those with hypertension.
研究领域:
药理学
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毒理学
·
心脏病学
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传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子