The neurotoxic effects of neonicotinoids (NEOs) have been widely reported in relation to the poisoning of wild birds, yet the underlying molecular mechanism has remained elusive. This study employed Japanese quails (Coturnix japonica) and primary quail embryonic neurons as in vivo and ex vivo models, respectively, to investigate the neurotoxic effects and mechanism of thiamethoxam (TMX), a representative neonicotinoid insecticide, at environmentally relevant concentrations. Following a 28-day exposure to TMX, metabolomic analysis of quail brain revealed TMX-induced changes in glutamatergic, GABA-ergic, and dopaminergic function. Subsequent ex vivo and in silico experimentation revealed that the activation of nicotinic acetylcholine receptors and calcium signaling, induced by clothianidin (CLO), the primary metabolite of TMX, served as upstream events for the alterations in neurotransmitter synthesis, metabolism, release, and uptake. Our findings propose that the disruption of the central nervous system, caused by environmentally significant concentrations of NEOs, may account for the avian poisoning events induced by NEOs.

As a phenylpyrazole insecticide, flufiprole is an important substitute for fipronil in the agricultural field of China. However, its bioaccumulation and metabolism in terrestrial organisms especially in the lizards living in the agricultural area have rarely been investigated. As an ectothermic animal, lizards are also sensitive to temperature changes. Considering global warming, this study measured bioaccumulation, metabolism, and hepatotoxicity of flufiprole in the Chinese native lizard (Eremias argus) under different temperature stresses. Lizards exposed to flufiprole-contaminated soil adsorbed flufiprole through the skin and flufiprole was preferred to accumulate in lizard liver and brain. The oxidation product fipronil sulfone was the main metabolite of flufiprole in both lizard liver and human liver microsomes, which were mainly metabolized by lizard CYP3A19 or human CYP3A4. The fipronil sulfone concentration increased with increased temperature in lizard tissues. In addition, more serious oxidative damage was shown under higher temperature as the glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in lizards increased with increased temperature after flufiprole exposure. Flufiprole exposure also induced lizard liver lesions, and these lesions became more serious in the higher-temperature groups. This study provided new insights into the risk assessment of flufiprole in lizards under global warming.

Tire wear particles (TWP) have become the major microplastic pollution in China. Road runoff containing TWP leachate can decrease the eye size and even induced mortality in the aquatic organisms. However, the toxic mechanism of TWP and road particles (RP) leachate on aquatic organisms is still unclear. In this study, the zebrafish embryos were exposed to TWP or RP leachate for 5 days at both environmental relevant and high concentrations. The adverse outcome pathways (AOPs) were screened from individual to molecular levels. The morphological and behavioral analysis demonstrated that the leachate exposure mainly impaired the eye development of zebrafish larvae and inhibited the larval swim behavior and phototactic response, which are the adverse outcomes. The phototransduction modulated by zebrafish retina was significantly down-regulated through transcriptomics and metabolomics analysis. The eye histopathological analysis showed that the decreased thickness of the retinal outer nuclear layer (ONL) and retinal pigmented epithelium (RPE) after leachate exposure were caused by the decreased photoreceptor cells. Moreover, the expression of NR2E3 and TPO genes showed concentration-dependent down-regulation after leachate exposure. The inhibition of photoreceptor cell proliferation was identified as the main reason for photoreceptor cell decrease in zebrafish larval eye. This study, for the first time, uncovered the underlying toxic mechanism of TWP and RP on zebrafish larval eyes.

Tetrachlorobisphenol A (TCBPA), a widely used halogenated flame retardant, is frequently detected in environmental compartments and human samples. However, unknown developmental toxicity and mechanisms limit the entire understanding of its effects. In this study, zebrafish (Danio rerio) embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics, behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential mechanisms. We found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor (ECM-receptor) interaction pathways through transcriptomic analysis. Behavioral and biochemical analysis results indicated abnormal swimming behavior of zebrafish larvae. Morphological observations revealed that TCBPA could cause the loss of head blood vessels. Metabolomic analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental toxicity. Our study demonstrated that by using omics, TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified.

Although the thyroid effects of pyrethroids on non-target organisms have been well studied, research on the toxic effects of pyrethorid metabolites is still limited. In this study, a type of representative Chinese lizards was used as the model and exposed to environmentally relevant concentrations of lambda-cyhalothrin (LCT) and 3-phenoxybenzoic acid (PBA) through cultivation on 3 and 15 μg/g soil to evaluate and compare their disruption effects on lizard hypothalamus-pituitary-thyroid (HPT) axis. The alterations occurred in lizards were examined through histopathology analyses, hormone level and gene expression measurements, the molecular binding interactions were analyzed in silico as well. The results showed that LCT exposure increased the plasma triiodothyronine (T3), thyroxine (T4) levels and the follicular epithelium heights of thyroid glands, whereas PBA induced no or much less degree of alterations. The ugt and dio2 gene expression in lizard liver was significantly up-regulated by LCT, but PBA caused less or opposite effects. The in silico homology simulation illustrated that LCT binds to TRα in the similar way of T3, while PBA binds to TRβ in the same manner of T3. The results demonstrated that both LCT and its metabolite-PBA could disrupt lizard HPT axis but through distinct mechanisms. The information would facilitate the comprehensive environmental safety assessment of pyrethroids.

Reptiles are sensitive to temperature changes as ectotherm animals. The climate warming may pose more serious threat to reptiles. Although the behavior effect and reproduction biology have been well studied, little information is available about the adaptation mechanisms of reptiles to temperature stress. In this study, the native Chinese species, Eremias argus were incubated at 15 (cold stress), 25 (control group) and 35 °C (thermal stress) for 24 h. The transcriptome and metabolome technology were applied to investigate the molecular regulation mechanisms of lizards to acute temperature changes. The CIRBP and HSPA8 were hub genes in response to temperature adaptation. The increased expression of PER gene in lizard circadian rhythm is associated with tyrosine metabolism after cold or thermal stress. The poly-unsaturated fatty acids in female lizard liver were significantly increased with up-regulation of FASN and ACACA genes after thermal stress, which proved the disruption of fatty acid biosynthesis pathway in corporation with the altered body weight. The cortisol and testosterone were important steroid hormones in response to temperature changes especially in male lizard liver. The increased CIRBP gene expression in lizard gonads suppressed the KDM6B gene, which regulates the testis development and may induce sex reversal in male lizard after thermal stress. The adaptation responses of lizards to temperature stress may threaten the health status of wild population.

Nowadays, the emergence of pesticides and its application in agriculture greatly improved the crop quality and food production. However, the resulted ecological problem caused by the widespread pesticide residues attracted more and more attention since the pesticides were harmful to most living organisms. Regulatory agencies such as Environmental Protection Agency (EPA) and European Chemicals Agency (ECHA) stipulated that a comprehensive pesticides risk assessment was essential and also underscored the application of computation method in evaluating pesticides. The present study aimed to use the Quantitative Structure-Activity Relationship (QSAR) method to establish models for quantitatively and qualitatively predicting the toxicity of pesticide against Skeletonema costatum. The regression model was developed using the Genetic Algorithm plus Multiple Linear Regression method and the classification model was established based on the Random Forest algorithm, respectively. Various internal and external validation metrics suggested that the obtained regression model was of good fitness (R2=0.722), robustness (Q2LOO=0.653) and external predictive ability (Q2Fn:0.719-0.776, CCC = 0.878). The classification could correctly predict 79.4% of pesticides in the training set and 69.7% in the validation set. The relatively high sensitivity value of the classification model indicated its good performance in identifying high-toxic pesticides. It could be concluded from the selected modelling descriptors that molecular weight and polarizability impacted the toxicity the most. The atom-type E-state descriptors generally contributed negatively to the pesticide toxicity which verified the negative influence of molecular hydrophilicity. Moreover, the lipophilic, carbon-type, charge related descriptors demonstrated the important influence of lipophilicity and polarity on pesticide toxicity. The models presented in this work could be used to pre-evaluate the toxicity of pesticides within the applicability domain, thus focusing resources on the high-toxic pesticides and assessing the environmental risk of pesticides quickly and economically.