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NEUROTOXICOLOGY · 2024 · IF 3.4

Evaluation of sub-chronic toxicity of melamine via systematic or oral delivery in adult zebrafish based on behavioral endpoints

Hsiu-Chao Chen,Wen-Wei Feng,Gilbert Audira,Kevin Adi Kurnia,San-Ho Hung,Agnes L. Castillo,Marri Jmelou M. Roldan,Chung-Der Hsiao,Chih-Hsin Hung

Melamine-tainted products have been found in the market and raised issues about food safety. Recent studies done in rodents and humans demonstrated the toxicities of melamine, especially in causing kidney damage and bladder stone formation. However, very few studies assessed its behavior toxicity in organisms, including fish. Therefore, in this study, the researchers aim to determine whether sub-chronic exposure to melamine via oral and systematic administration could induce behavioral abnormality in zebrafish. After 14 days of systematic exposure to melamine at doses of 0.1 and 10 ppm levels, zebrafish were subjected to multiple behavioral assays. Results from both exposure routes showed that melamine indeed slightly increased fish locomotion and altered their exploratory behaviors in the novel tank assay. Furthermore, tightened shoaling formation was also displayed by the treated fish in the waterborne exposure group. However, melamine exposure did not cause any obvious alterations in fish behaviors during other behavioral tests. In addition, in comparison with previously published data on the behavior toxicities of several solvents in zebrafish, our phenomic analysis suggests the relatively low behavior toxicities of melamine via either systematic exposure or oral administration to zebrafish compared to those solvents. Nevertheless, our data indicate that the potential neurotoxicity of chronic low-dose melamine should not be ignored.

CAS / MDL: 108-78-1
研究领域: 毒理学 · 行为生物学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2024 · IF 8.2

Highly sensitive response to the toxicity of environmental chemicals in transparent casper zebrafish

Yingjun Xu,Yiming Han,Li Liu,Shanshan Han,Shibiao Zou,Bo Cheng,Fengbang Wang,Xunwei Xie,Yong Liang,Maoyong Song,Shaochen Pang

The response sensitivity to toxic substances is the most concerned performance of animal model in chemical risk assessment. Casper (mitfa w2/w2 ;mpv17 a9/a9 ) , a transparent zebrafish mutant, is a useful in vivo model for toxicological assessment. However, the ability of casper to respond to the toxicity of exogenous chemicals is unknown. In this study, zebrafish embryos were exposed to five environmental chemicals, chlorpyrifos, lindane, α-endosulfan, bisphenol A, tetrabromobisphenol A (TBBPA), and an antiepileptic drug valproic acid. The half-lethal concentration (LC 50 ) values of these chemicals in casper embryos were 62–87 % of that in the wild-type. After TBBPA exposure, the occurrence of developmental defects in the posterior blood island of casper embryos was increased by 67–77 % in relative to the wild-type, and the half-maximal effective concentration (EC 50 ) in casper was 73 % of that in the wild-type. Moreover, the casper genetic background significantly increased the hyperlocomotion caused by chlorpyrifos and lindane exposure compared with the wild-type. These results demonstrated that casper had greater susceptibility to toxicity than wild-type zebrafish in acute toxicity, developmental toxicity and neurobehavioral toxicity assessments. Our data will inform future toxicological studies in casper and accelerate the development of efficient approaches and strategies for toxicity assessment via the use of casper .

研究领域: 毒理学 · 环境科学 · 生物学
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SCIENCE OF THE TOTAL ENVIRONMENT · 2022 · IF 10.753

New evidence for neurobehavioral toxicity of deltamethrin at environmentally relevant levels in zebrafish

Lei Lei,Biran Zhu,Kun Qiao,Yuxi Zhou,Xiangping Chen,Jun Men,Lihua Yang,Qidong Wang,Jian Han,Bingsheng Zhou

Deltamethrin, a widely used type II pyrethroid insecticide, was reported with neurotoxicity to aquatic organisms, such as fish. However, the effects and potential mechanisms on the central nervous system remain largely unknown, especially under environmental concentrations. Therefore, we exposed adult female zebrafish to environmentally relevant levels of deltamethrin (30, 100, and 333 ng/L) for 21 days to assess neurobehavioral changes related to the central nervous system and explore the modes of action. Behavioral assays revealed significant increases in the swimming speeds, residence time near other fish and the shoaling cohesion in exposed fish. Transcriptomic results enriched the disrupted neural functions involving the glutamatergic and dopaminergic synapses in the brain. The qRT-PCR confirmed the upregulation of the factors for promoting the glutamate release. The measurement of neurotransmitters showed significantly increased content of the excitatory neurotransmitter glutamate in the brain. Taken together, deltamethrin exposure increased the glutamate level and promoted the release of such an excitatory neurotransmitter between the glutamatergic synapses in the brain, which eventually led to hyperactivity of social behaviors in adult zebrafish.

CAS / MDL: 52918-63-5
研究领域: 环境科学 · 神经科学 · 毒理学
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2025 · IF 11.3

Developmental and Neurobehavioral Toxicity of Hexaphenoxycyclotriphosphazene: Implications for Its Safety as a Flame-Retardant Alternative to Triphenyl Phosphate

Ruobing Bai,Hongyi Xian,Yu Feng,Xiyun Huang,Shiyue Tang,Zhiming Li,Long Zhang,Yizhou Zhong,Wanyan Wu,Jiangpeng Tang,Chudan Gao,Li Yan,Xinguang Zhong,Da Chen,Zhenlie Huang

Hexaphenoxycyclotriphosphazene (HPCTP) has been introduced as a halogen-free replacement for the flame-retardant triphenyl phosphate (TPhP); however, its environmental behavior and toxicological safety remain poorly defined. Here, using zebrafish larvae with TPhP as a benchmark, we systematically evaluated the developmental and neurobehavioral toxicity of HPCTP at environmentally relevant concentrations (50–5000 ng/L) from 6 to 120 h postfertilization. HPCTP showed greater bioaccumulation potential than TPhP, suggesting the risk of long-term ecological persistence. Despite lower acute toxicity, HPCTP induced pronounced developmental defects, including reduced body length and cardiac malformations. Strikingly, HPCTP and TPhP produced divergent neurobehavioral outcomes. HPCTP caused dose-dependent depression-like behaviors (hypoactivity, light-zone avoidance) through suppression of serotonin 1A (5-HT1A) signaling, supported by decreased htr1aa expression and serotonin levels and partially rescued by the 5-HT1A receptor agonist 8-OH-DPAT. By contrast, TPhP elicited anxiety-like phenotypes (hyperactivity, thigmotaxis) via CD83-dependent neuroinflammation, evidenced by decreased cd83 expression and microglial activation, which were reversed by cd83 overexpression. Taken together, these findings demonstrate that HPCTP, though marketed as a safer alternative, poses distinct developmental and neurobehavioral hazards, underscoring the urgent need for comprehensive risk evaluation prior to its widespread application.

研究领域: 环境毒理学 · 发育生物学 · 神经科学 · 分子药理学 · 生态风险评估
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY · 2024 · IF 3.9

Time-series variation in the locomotor behavior and vocal traits of Japanese medaka (Oryzias latipes) acutely exposed to organophosphorus pesticide chlorpyrifos

Mengcheng Zhuo,Xi Wang,Yanhong Shi,Kun Chen,Xuchun Qiu

Organophosphorus pesticides (OPs), such as chlorpyrifos (CPF), are the most commonly used pesticides worldwide. Considering that OPs will eventually enter aquatic ecosystems due to runoff from agricultural lands, accidental leakage, and other unforeseen emergencies, monitoring water pollution of those substances is crucial for environmental protection and public health. In this study, Japanese medaka ( Oryzias latipes ) were exposed to CPF (0.03, 0.06, and 0.12 mg/L) for 6 h, and the time-series variations in their locomotor behavior and vocal traits were investigated. Compared with that measured before exposure, significantly changed locomotor behavior and vocal traits in Japanese medaka exposed to CPF could be observed at 4 h after exposure and thereafter, and the pattern of behavioral changes depends on the CPF concentrations. Exposure to CPF also changed the frequency-sound pressure level curve of Japanese medaka at 6 h after exposure, especially at 0.12 mg/L. Moreover, CPF exposure could significantly inhibit the acetylcholinesterase (AChE) activity in the brains and eyes of medaka, which exhibited significant correlations with the variation of locomotor behavioral and vocal traits. Considering that inhibiting the AChE activity is the primary mechanism underlying the neurobehavioral toxicity of all OPs, our finding suggested that simultaneously monitoring changes in the locomotor behavioral and vocal traits has a high potential to reflect the pollution of organophosphorus substances.

CAS / MDL: 2921-88-2
研究领域: 环境科学 · 毒理学 · 水生生物学 · 生态毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Exposure to thimerosal induces behavioral abnormality in the early life stages of zebrafish via altering amino acid homeostasis

Xuchun Qiu,Yibing Zhang,Jiarui Gao,Yiming Cui,Kejun Dong,Kun Chen,Yanhong Shi

Thimerosal (THI) has become a significant source of organic mercury pollutants in aquatic ecosystems, but there is limited information regarding its adverse effects on fish. In this study, zebrafish embryos were exposed to THI at 0 (control), 5.0, and 50 ng/L from 0–5 days post fertilization (dpf), and variations in their survival, development, behavior, free amino acid contents, and the biochemical responses involved in monoaminergic systems were examined. Although THI exposure did not significantly affect the survival, heart rate, or hatching time of zebrafish embryos, it substantially increased swimming velocity (136–154 % of the control) and reduced exploratory behavior (141–142 % of the control) in zebrafish larvae at 5 dpf. Exposure also significantly altered the amino acid contents (51–209 % of the control) and monoamine levels (70–154 % of the control) in zebrafish larvae, some of which displayed significant correlations with behavioral traits. THI significantly elevated dopamine receptor gene expression and monoamine oxidase activity in zebrafish larvae. Adding extra phenylalanine or tryptophan to the E3 medium facilitates the recovery of zebrafish larvae from the abnormal behaviors induced by THI. These findings reveal for the first time that THI exposure at the level of ng/L is sufficient to induce neurobehavioral toxic effects in the early life stages of zebrafish, and disrupting amino acid homeostasis is a critical underlying mechanism. This study provides valuable insights into the toxicity of THI to fish and highlights the importance of assessing its potential risks to aquatic ecosystems.

研究领域: 环境毒理学 · 水生生物学 · 神经科学 · 发育生物学
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