JOURNAL OF APPLIED TOXICOLOGY
·
2015
·Vol. 35
·期 11
·1415-1426
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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
CHEMOSPHERE
·
2017
·
IF 4.208
Zhuang Wang,Fan Zhang,Se Wang,Willie J.G.M. Peijnenburg
Graphene and ionic liquids (ILs) released into the environment will interact with each other. So far however, the risks associated with the concurrent exposure of biota to graphene and ILs in the environment have received little attention. The research reported here focused on observing and predicting the joint toxicity effects in the green alga Scenedesmus obliquus exposed to binary mixtures of intrinsic graphene (iG)/graphene oxide (GO) and five ILs of varying anionic and cationic types. The isolated ILs in the binary mixtures were the main contributors to toxicity. The binary GO-IL mixtures resulted in more severe joint toxicity than the binary iG-IL mixtures, irrespective of mixture ratios. The mechanism of the joint toxicity may be associated with the adsorption capability of the graphenes for the ILs, the dispersion stability of the graphenes in aquatic media, and modulation of the binary mixtures-induced oxidative stress . A toxic unit assessment showed that the graphene and IL toxicities were additive at low concentration of the mixtures but antagonistic at high concentration of the mixtures. Predictions made using the concentration addition and independent action models were close to the observed joint toxicities regardless of mixture types and mixture ratios. These findings provide new insights that are of use in the risk assessment of mixtures of engineered nanoparticles and other environmentally relevant contaminants.
研究领域:
环境科学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2022
·
IF 4.966
Dong Guo,Lulu Luo,Yuan Kong,Zhiyang Kuang,Siyi Wen,Meirong Zhao,Weiguang Zhang,Jun Fan
Paclobutrazol is a widely used chiral plant growth regulator and its enantioselective toxicity in aquatic organisms is less explored till now. Herein, the enantioselective neurotoxicity of paclobutrazol mediated by oxidative stress in zebrafish were investigated. The oxidative stress parameters and neurotoxic biomarkers changed significantly in each exposure group, and paclobutrazol showed enantioselective toxicity in zebrafish. Firstly, (2 R , 3 R )-paclobutrazol exhibited a stronger oxidative stress in zebrafish than (2 S , 3 S )-enantiomer ( P < 0.05). Then, activities of acetylcholinesterase , calcineurin , and total nitric oxide synthase in (2 R , 3 R )-paclobutrazol treatments were 0.61–0.89, 1.24–1.53, and 1.21–1.35-fold stronger ( P < 0.05) than those in (2 S , 3 S )-enantiomer treatments, respectively. Next, the content variations of four neurotransmitters in zebrafish exposed to (2 R , 3 R )-paclobutrazol were significantly larger than those in (2 S , 3 S )-enantiomer treatments ( P < 0.05). Moreover, (2 R , 3 R )-paclobutrazol had stronger binding with the receptors than (2 S , 3 S )-enantiomer through molecular docking . The integrated biomarker response values further demonstrated that (2 R , 3 R )-paclobutrazol showed stronger toxicity to zebrafish than (2 S , 3 S )-enantiomer. Furthermore, the neurotoxicity of paclobutrazol can be interpreted as the mediating effect of oxidative stress in zebrafish through correlation analysis, and an adverse outcome pathway for the nervous system in zebrafish induced by paclobutrazol was proposed. This work will greatly extend our understanding on the enantioselective toxic effects of paclobutrazol in aquatic organisms.
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
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xiangmei Xiang,Juanjuan Zhou,Shaochen Lin,Nan Zhang,Gulizhabaier Abulipizi,Guikui Chen,Zhanjun Li
Microplastics (MPs) can adsorb and influence the toxicity of traditional pollutants significantly. Although the complex toxicity of MPs and molecular pollutants were frequently reported, rare work has been done on the influence of MPs on the phototoxicity of photosensitive pollutants under light illumination condition. Herein, polystyrene microplastics (PS) (~1 μm in diameter, 5.0 mg/L) was used as a model MP to investigate its influence on the phototoxicity of a soluble blue dye, methylene blue (MB) using Daphnia magna as a model organism. The results indicate that PS could adsorb MB effectively and quickly, thus led to concentrated MB on PS/water interface. D. magna ingested MB-adsorbed PS very quickly within tens of minutes. Although MB or PS alone led to negligible lethal phototoxicity to D. magna , PS significantly enhanced the lethal phototoxicity of MB (0.25 mg/L) to D. magna after light illumination (10 h) with the survival rate decreased by 63.3 % compared with the control in the dark. Further, the phototoxicity of MB was found positively consistent with PS concentration from 0.50 mg/L to 7.50 mg/L. The singlet oxygen fluorescence assay indicates that the presence of PS did not increase the total amount of singlet oxygen in the aquatic environment but increased the local concentration in the gut area via non-selective ingestion of D. magna . High level singlet oxygen generated in the gut might possibly be the main reason that led to the massive death of D. magna . Surface adsorption of photosensitive pollutants may transform inert MPs into persistent solid sources of singlet oxygen production and become a new potential lethal threat to aquatic small organisms and ecological equilibrium. This kind of MPs and light dual drive phototoxicity of photosensitive pollutants needs to paid more attention in understanding the uncertain ecological risk of MPs.
研究领域:
环境科学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Zhaochuan Li,Hao Zhou,Yang Liu,Jingjing Zhan,Wentao Li,Kaiming Yang,Xianliang Yi
Dibutyl phthalate (DBP) is a commonly used additive in plastic products, so it may potentially coexist with microplastics (MPs) in marine environment. The ingestion of MPs might affect the accumulation of DBP in marine organisms. In this study, the marine copepod Tigriopus japonicus was applied to study the combined effect of DBP and polystyrene microplastics (mPS) on the copepod through both acute mortality tests and chronic reproduction tests. The LC 50 of DBP was 1.23 mg L −1 (95% CI: 1.11–1.35 mg L −1 ), while exposure to mPS didn’t have significant lethal effect on the copepods. Adsorption to MPs led to decreased bioavailability of DBP, resulting in decreased toxicity of DBP. In contrast to the results of acute toxicity tests , DBP didn’t affect the reproduction of the copepods at lower exposure concentrations, while mPS reduced the number of nauplii and extended the time to hatch. Similar as acute toxicity tests, antagonistic interaction was observed for mPS and DBP in chronic reproduction tests, which might be attributed to promoted aggregation of mPS at presence of DBP. Overall, antagonistic toxicity effect between the two pollutants was observed for both acute and chronic tests, but the mechanisms of the interaction between DBP and mPS were different. Results of the present study highlighted the importance of long-term exposure when evaluating the toxic effect of MPs and their combined effect with other chemicals.
研究领域:
环境科学
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海洋生物学
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DOI
PubMed
高影响因子
XENOBIOTICA
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2017
·
IF 1.932
Hui Li,Dongju Lin,Ying Peng,Jiang Zheng
1. Nitrofurantoin (NFT), a 5-nitrofuran derivative, has been widely used for the treatment of specific urinary tract infections. It has been reported that exposure to NFT was associated with various adverse effects, particularly hepatotoxicity and pneumotoxicity. The objective of the study was to identify reactive metabolites of NFT and explore the mechanisms of the toxicities.2. An epoxide intermediate generated in microsomal incubations was trapped by glutathione (GSH) and 4-bromobenzyl mercaptan (BBM), and the resulting GSH and BBM conjugates were characterized by LC–MS/MS. A spontaneous denitration took place in the trapping reaction. 2-Nitrofuran and 2-hydroxyfuran as model compounds were employed to probe the mechanism of the denitration.3. The oxidative activation of NFT was P450-dependent, and P450 3A5 and P450 2A6 were the principal enzymes responsible for the bioactivation. The findings facilitate the understanding of the mechanisms of NFT-induced toxicities.
研究领域:
药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Journal of Xenobiotics
·
2024
·Vol. 14
·期 2
·452-466
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IF 6.8
Bingying Li,Yongsi Huang,Duan Pi,Xiang Li,Yafen Guo,Zhiying Liang,Xiaohong Song,Junjie Wang,Xuegeng Wang
Bisphenol S (BPS), one of the substitutes for bisphenol A (BPA), is widely used in various commodities. The BPS concentrations in surface water have gradually increased in recent years, making it a predominant bisphenol analogue in the aquatic environment and raising concerns about its health and ecological effects on aquatic organisms. For this study, we conducted a 96 h acute toxicity test and a 15-day developmental exposure test to assess the adverse effects of BPS exposure in Chinese medaka (Oryzias sinensis), a new local aquatic animal model. The results indicate that the acute exposure of Chinese medaka embryos to BPS led to relatively low toxicity. However, developmental exposure to BPS was found to cause developmental abnormalities, such as decreased hatching rate and body length, at 15 dpf. A transcriptome analysis showed that exposure to different concentrations of bisphenol S often induced different reactions. In summary, environmental concentrations of BPS can have adverse effects on the hatching and physical development of Chinese medaka, and further attention needs to be paid to the potential toxicity of environmental BPS.
研究领域:
环境科学
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毒理学
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生态学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
·
IF 6.1
Xiaoran Xue,Zaiqiu Zhang,Yang Yang,Lin Hu,Mingyi Zhao,Qingnan He
Objective This study aimed to assess the acute developmental toxicity of perchlorate exposure and identify its manifestation of neurotoxicity in zebrafish (Danio rerio) model. Methods Zebrafish larvae were exposed to sodium perchlorate at early developmental stages and the phenotypes of various developmental abnormalities were observed and recorded. Neurodevelopmental toxicity has been studied in particular in terms of central nervous system apoptosis, peripheral motor abnormalities, and abnormal autonomic motor behavior. Samples were processed for pathological, transcriptomic, and PCR analyses. Results Acute exposure of zebrafish larvae to perchlorate resulted in developmental toxicity in a concentration-dependent manner. Heart rate abnormality (33 %), slow blood flow (37 %), abnormal size of liver (23 %), delayed yolk absorption (70 %), and abnormal body pigmentation (100 %) were observed in the 3.83 mg/mL group. Heart edema (10 %), heart rate abnormality (60 %), slow blood flow (67 %), abnormal size of liver (77 %), delayed yolk absorption (100 %), abnormalities in intestinal morphology (30 %), abnormal body pigmentation (100 %), and shorter body length (47 %) were observed in the 4.03 mg/mL group. Developmental neurotoxicity was characterized by brain apoptosis, damage to the central nervous system ( P < 0.01) and peripheral motor neurons ( P < 0.0001), and reduced autonomous motor distance ( P < 0.01). Transcriptomic analysis revealed that c3a.1, c5, fga, fgb, and fgg were upregulated in the complement and coagulation cascades, and the mRNA levels of c3a.1, dusp1, slc2a6, purba, and klf9 were found upregulated in PCR. Conclusion Acute perchlorate exposure on zebrafish larvae caused various developmental toxicity in a concentration-dependent manner, notably neurotoxicity. We believed the immunological and inflammatory responses were involved.
研究领域:
毒理学
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发育生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Toxics
·
2025
·Vol. 13
·期 2
·122
·
IF 4.1
Yixiao Wu,Wenjing Yu,Zhenyan Song,Jiawei He,Ze Li,Qi Chen,Shiwei Wang,Ping Li,Shaowu Cheng
Emerging contaminants refer to chemical substances that have not been widely regulated but possess the potential to cause adverse effects on both the environment and human health. Antibiotics, as emerging contaminants, pose significant threats to ecosystems and human health due to their widespread use and persistence in the environment. Levofloxacin, a broad-spectrum fluoroquinolone antibiotic, is commonly employed in the treatment of bacterial infections, and has been frequently detected in environmental matrices and freshwater systems. In this study, we assessed the effects of levofloxacin on hatchability, mortality rates, malformations, behavioral changes, and cardiac development in zebrafish embryos by exposing them to varying concentrations of levofloxacin (0, 0.5, 1, 2, 4, and 8 mM). Our results demonstrate that levofloxacin exposure significantly impaired the growth and development of zebrafish larvae, particularly at higher concentrations. Notable effects included reduced body length, abnormal yolk sac and swim bladder development, pericardial edema, prolonged distances between the sinus venosus and arteriolar bulb (SV-BA), and disruptions in heart rate. Quantitative PCR analysis further revealed that levofloxacin exposure significantly upregulated the expression of key cardiac development genes in zebrafish larvae, includingnppa,myh6,cacna1ab,myl7,gata4,nkx2.5,tbx2b, andtbx5b. These findings indicate that levofloxacin exposure exerts significant toxic effects on both embryonic and larval growth as well as heart development and gene expression in zebrafish. This study provides critical insights into the potential ecological risks posed by levofloxacin along with other antibiotics while laying a foundation for further investigation into their toxicological mechanisms.
研究领域:
环境科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Life-Basel
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2024
·Vol. 14
·期 5
·544
·
IF 3.2
Hao Wu,Xiping Yuan,Xing Tian,Jinwei Gao,Min Xie,Zhonggui Xie,Rui Song,Dongsheng Ou
Niclosamide (NIC) is a potent salicylanilide molluscicide/helminthicide commonly utilized for parasite and mollusc control in aquatic environments. Due to its persistent presence in water bodies, there is growing concern regarding its impact on aquatic organisms, yet this remains inadequately elucidated. Consequently, this study aims to assess the hepatotoxic effects and detoxification capacity of black carp (Mylopharyngodon piceus) in a semi-static system, employing various parameters for analysis. NIC was applied to juvenile black carp at three different concentrations (0, 10 and 50 μg/L) for 28 days in an environmentally realistic manner. Exposure to 50 μg/L NIC resulted in an increase in hepatic lysozyme (LYZ), alkaline phosphatase (ALP), and complement 4 (C4) levels while simultaneously causing a decrease in peroxidase (POD) activity. Additionally, NIC exposure exhibited a dose-dependent effect on elevating serum levels of LYZ, ALP, complement 3 (C3), C4, and immunoglobulin T (IgT). Notably, the mRNA levels of immune-related genestnfα,il8, andil6, as well asnrampandleap2, were upregulated in fish exposed to NIC. RNA-Seq analysis identified 219 differentially expressed genes (DEGs) inM. piceusafter NIC exposure, with 94 upregulated and 125 downregulated genes. KEGG and GO analyses showed enrichment in drug metabolism pathways and activities related to oxidoreductase, lip oprotein particles, and cholesterol transport at 50 μg/L NIC. Additionally, numerous genes associated with lipid metabolism, oxidative stress, and innate immunity were upregulated in NIC-exposedM. piceus. Taken together, these findings indicate that NIC has the potential to cause hepatotoxicity and immunotoxicity inM. piceus. This research offers important insights for further understanding the impact of molluscicide/helminthicide aquatic toxicity in ecosystems.
研究领域:
环境科学
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毒理学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 111
·91398-91406
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IF 3.84
Xiao Zheng,Dan Shao,Jing Li,Yubin Song,Yujing Chen,Yue Pan,Shoujun Zhu,Bai Yang,Li Chen
Carbon dots (CDs) have recently emerged as a new class of fluorescent nanomaterials and are already competitive in many respects to conventional semiconductor quantum dots (QDs). Despite CDs remarkable advantages in bioimaging, biosensing and other biomedical applications, their biosafety is still unclear. In the present study, the systematic single and repeated dose toxicity and biodistribution of two citric acid-based probes (CDs and a derivative, Et-IPCA) were investigated in vivo. For the single dose toxicity studies, the lethal dose 50 (LD50) of CDs was 391.615 mg kg−1 and 357.771 mg kg−1 for female and male mice, respectively, while Et-IPCA reached its saturation point in solution at 25 mg kg−1 and did not lead to the death of any mice at that concentration. For the repeated dose toxicity studies, although there were temporary changes in hematological parameters suggesting an acute inflammatory response after seven doses, the data on the body weight, organ coefficients, hematological parameters, blood biochemistry, and organ histopathology at the end of the 90 day recovery period suggested that both the CDs and Et-IPCA had low toxicity over the 90 day period. These findings will be useful for the future development of CDs-based drug delivery systems and for the development of clinical applications of these systems.
研究领域:
生物医学
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毒理学
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纳米材料科学
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产品关联
DOI
高影响因子
Foods
·
2023
·Vol. 12
·期 13
·2555
·
IF 5.2
Song Yu,Lianpeng Zou,Jiawei Zhao,Yiping Zhu
Human health is seriously threatened by mycotoxin contamination, yet health risk assessments are typically based on just one mycotoxin, potentially excluding the additive or competitive interactions between co-occurring mycotoxins. In this investigation, we evaluated the individual or combined toxicological effects of three fumonisin-family B mycotoxins: fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), by using porcine intestinal epithelial cells (IPEC). IPEC cells were exposed to various concentrations (2.5–40 μM) for 48 h, and a cell counting kit (CCK8) was used to determine cell vitality. Firstly, we discovered that they might inhibit cell viability. Additionally, the cytotoxicity of FB1 was significantly greater than that of FB2 and FB3. The results also indicated that the combinations of FB1-FB2, FB2-FB3, and FB1-FB2-FB3 showed synergistically toxicological effects at the ID10-ID50 levels and antagonistic effects at the ID75-ID90 levels. In addition, the FB1-FB3 exposure was also synergistic at the ID10-ID25 level. We also found that myriocin and resveratrol alleviated the cytotoxicity induced by fumonisin in IPEC cells. In all, this study may contribute to the determination of legal limits, the optimization of risk assessment for fumonisins in food and feed, and the development of new methods to alleviate fumonisin toxicity.Keywords:fumonisins;gastrointestinal toxicity;combined toxicity;risk assessment;control strategy
研究领域:
毒理学
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食品安全
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兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）