Due to worldwide production, sales and application, neonicotinoids dominate the global use of insecticides. While, neonicotinoids are considered as pinpoint neurotoxicants that impair cholinergic neurotransmission in pest insects, the sublethal effects on nontarget organisms and other neurotransmitters remain poorly understood. Thus, we investigated long-term neurological outcomes in the decomposer nematode Caenorhabditis elegans. In the adult roundworm the neonicotinoid thiacloprid impaired serotonergic and dopaminergic neuromuscular behaviors, while respective exposures to thiamethoxam showed no effects. Thiacloprid caused a concentration-dependent delay of the transition between swimming and crawling locomotion that is controlled by dopaminergic and serotonergic neurotransmission. Age-resolved analyses revealed that impairment of locomotion occurred in young as well as middle-aged worms. Treatment with exogenous serotonin rescued thiacloprid-induced swimming deficits in young worms, whereas additional exposure with silica nanoparticles enhanced the reduction of swimming behavior. Delay of forward locomotion was partly caused by a new paralysis pattern that identified thiacloprid as an agent promoting a specific rigidity of posterior body wall muscle cells and peripheral neuropathy in the nematode (lowest-observed-effect-level 10 ng/ml). On the molecular level exposure with thiacloprid accelerated protein aggregation in body wall muscle cells of polyglutamine disease reporter worms indicating proteotoxic stress. The results from the soil nematode Caenorhabditis elegans show that assessment of neurotoxicity by neonicotinoids requires acknowledgment and deeper research into dopaminergic and serotonergic neurochemistry of nontarget organisms. Likewise, it has to be considered more that different neonicotinoids may promote diverse neural end points.

Fumonisin B1 (FB1) is a neurodegenerative mycotoxin synthesized by Fusarium spp., but the potential neurobehavioral toxicity effects in organisms have not been characterized clearly. Caenorhabditis elegans (C. elegans) has emerged as a promising model organism for neurotoxicological studies due to characteristics such as well-functioning nervous system and rich behavioral phenotypes. To investigate whether FB1 has neurobehavioral toxicity effects on C. elegans, the motor behavior, neuronal structure, neurotransmitter content, and gene expression related with neurotransmission of C. elegans were determined after exposed to 20–200 μg/mL FB1 for 24 h and 48 h, respectively. Results showed that FB1 caused behavioral defects, including body bends, head thrashes, crawling distance, mean speed, mean amplitude, mean wavelength, foraging behavior, and chemotaxis learning ability in a dose-, and time-dependent manner. In addition, when C. elegans was exposed to FB1 at a concentration of 200 μg/mL for 24 h and above 100 μg/mL for 48 h, the GABAergic and serotonergic neurons were damaged, but no effect on dopaminergic, glutamatergic, and cholinergic neurons. The relative content of GABA and serotonin decreased significantly. Furthermore, abnormal expression of mRNA levels associated with GABA and serotonin were found in nematodes treated with FB1, such as unc-30, unc-47, unc-49, exp-1, mod-5, cat-1, and tph-1. The neurobehavioral toxicity effect of FB1 may be mediated by abnormal neurotransmission of GABA and serotonin. This study provides useful information for understanding the neurotoxicity of FB1.

Carcinogenic and neurotoxic polybrominated diphenyl ethers (PBDEs) are environmentally ubiquitous and have been widely investigated. However, little is understood regarding their pollution status, sources, and potential risk to persons in public transportation microenvironments (PTMs). We collected 60 dust samples from PTMs and then selected four materials typical of bus interiors to determine the sources of PBDEs in dust using principal component analysis coupled with Mantel tests. We then evaluated the risk of PBDEs to public health using Monte Carlo simulations. We found that PBDE concentrations in dust were 2-fold higher in buses than at bus stops and that brominated diphenyl ether (BDE)-209 was the main pollutant. The number of buses that passed through a bust stop contributed to the extent of PBDE pollution, and the primary potential sources of PBDEs in dust were plastic handles and curtains inside buses; BDE-209 and BDE-154 were the main contributors of pollution. We found that health risk was 8-fold higher in toddlers than in adults and that the reference doses of PBDEs in dust were far below the United States Environmental Protection Agency limits. Our findings provide a scientific basis that may aid in preventing PBDE pollution and guiding related pollution management strategies in PTMs.

The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 μg/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, α1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, α1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.

Mercury (Hg), a potent neurotoxic element, can biomagnify through food webs once converted into methylmercury (MeHg). Some studies have found that selenium (Se) exposure may reduce MeHg bioaccumulation and toxicity, though this pattern is not universal. Se itself can also be toxic at elevated levels. We experimentally manipulated the relative concentrations of dietary MeHg and Se (as selenomethionine [SeMet]) for an aquatic grazer (the mayfly, Neocloeon triangulifer) and its food source (diatoms). Under low MeHg treatment (0.2 ng/L), diatoms exhibited a quadratic pattern, with decreasing diatom MeHg concentration up to 2.0 μg Se/L and increasing MeHg accumulation at higher SeMet concentrations. Under high MeHg treatment (2 ng/L), SeMet concentrations had no effect on diatom MeHg concentrations. Mayfly MeHg concentrations and biomagnification factors (concentration of MeHg in mayflies: concentration of MeHg in diatoms) declined with SeMet addition only in the high MeHg treatment. Mayfly MeHg biomagnification factors decreased from 5.3 to 3.3 in the high MeHg treatment, while the biomagnification factor was constant with an average of 4.9 in the low MeHg treatment. The benefit of reduced MeHg biomagnification was offset by non-lethal effects and high mortality associated with ‘protective’ levels of SeMet exposure. Mayfly larvae escape behavior (i.e., startle response) was greatly reduced at early exposure days. Larvae took nearly twice as long to metamorphose to adults at high Se concentrations. The minimum number of days to mayfly emergence did not differ by SeMet exposure, with an average of 13 days. We measured an LC50SₑMₑₜ for mayflies of 3.9 μg Se/L, with complete mortality at concentrations ≥6.0 μg Se/L. High reproductive mortality occurred at elevated SeMet exposures, with only 0–18% emergence at ≥4.12 μg Se/L. Collectively, our results suggest that while there is some evidence that Se can reduce MeHg accumulation at the base of the food web at specific exposure levels of SeMet and MeHg, Se is also toxic to mayflies and could lead to negative effects that extend across ecosystem boundaries.

Triclosan (TCS), an emergent pollutant, is raising a global concern due to its toxic effects on organisms and aquatic ecosystems. The non-availability of proven treatment technologies for TCS remediation is the central issue stressing thorough research on understanding the underlying mechanisms of toxicity and assessing vital biomarkers in the aquatic organism for practical monitoring purposes. Given the unprecedented circumstances during COVID 19 pandemic, a several-fold higher discharge of TCS in the aquatic ecosystems cannot be considered a remote possibility. Therefore, identifying potential biomarkers for assessing chronic effects of TCS are prerequisites for addressing the issues related to its ecological impact and its monitoring in the future. It is the first holistic review on highlighting the biomarkers of TCS toxicity based on a comprehensive review of available literature about the biomarkers related to cytotoxicity, genotoxicity, hematological, alterations of gene expression, and metabolic profiling. This review establishes that biomarkers at the subcellular level such as oxidative stress, lipid peroxidation, neurotoxicity, and metabolic enzymes can be used to evaluate the cytotoxic effect of TCS in future investigations. Micronuclei frequency and % DNA damage proved to be reliable biomarkers for genotoxic effects of TCS in fishes and other aquatic organisms. Alteration of gene expression and metabolic profiling in different organs provides a better insight into mechanisms underlying the biocide's toxicity. In the concluding part of the review, the present status of knowledge about mechanisms of antimicrobial resistance of TCS and its relevance in understanding the toxicity is also discussed referring to the relevant reports on microorganisms.

Mercury (Hg) is a neurotoxic element with severe effects on humans and wildlife. Widely distributed by atmospheric deposition, it can also be localized near point sources such as mines. Mercury has been shown to reduce the reproduction of bird populations in field observations in North America and Europe, but studies are needed in Asia, where the majority of emissions now occur. We investigated the reproduction of two passerines, Japanese Tit (Parus minor) and Russet Sparrow (Passer rutilans), in a large-scale Hg mining district, and a non-mining district, both in Guizhou, southwest China. Concentrations of Hg were elevated in the mining district (blood levels of 2.54 ± 2.21 [SD] and 0.71 ± 0.40 μg/g, in adult tits and sparrows, respectively). However, we saw no evidence of decreased breeding there: metrics such as egg volume, nestling weight, hatching and fledgling success, were all similar between the different districts across two breeding seasons. Nor were there correlations at the mining district between Hg levels of adults or juveniles, and hatching or fledgling success, or nestling weight. Nest success was high even in the mining district (tit, 64.0%; sparrow: 83.1%). This lack of reproductive decline may be related to lower blood levels in nestlings (means < 0.15 μg/g for both species). Concentrations of selenium (Se), and Se-to-Hg molar ratio, were also not correlated to breeding success. Although blood levels of 3.0 μg/g have been considered as a threshold of adverse effects in birds, even leading to severe effects, we detected no population-level reproductive effects, despite ~25% of the adult tits being above this level. Future work should investigate different locations in the mining district, different life-stages of the birds, and a wider variety of species. The hypothesis that bird populations can evolve resistance to Hg in contaminated areas should also be examined further.

As emerging pollutants, microplastics (MPs) have been found globally in various freshwater and marine matrices. This study recompiled 270 endpoints of 3765 individuals from 43 publications, reporting the onset of enhanced biological performance and reduced oxidative stress biomarkers induced by MPs in aquatic organisms at environmentally relevant concentrations (≤1 mg/L, median = 0.1 mg/L). The stimulatory responses of consumption, growth, reproduction and survival ranged from 131% to 144% of the control, with a combined response of 136%. The overall inhibitory response of 9 oxidative stress biomarkers was 71% of the control, and commonly below 75%. The random-effects meta-regression indicated that the extents of MPs-induced responses were independent of habitat, MP composition, morphology, particle size and exposure duration. The results implied that the exposure to MPs at low and high concentrations might induce opposite/non-monotonic responses in aquatic biota. Correspondingly, the hormetic dose response relationships were found at various endpoints, such as reproduction, genotoxicity, immunotoxicity, neurotoxicity and behavioral alteration. Hormesis offers a novel perspective for understanding the dose response mode of aquatic organisms exposed to low and high concentrations of MPs, highlighting the necessity to incorporate the hormetic dose response model into the ecological/environmental risk assessment of MPs.

Paraquat (PQ) is one of the most widely used herbicides in the world due to its excellent weed control effects. Accumulating evidence has revealed that long-term exposure to PQ can significantly increase the risk of Parkinson’s disease (PD). However, the underlying molecular mechanisms are yet to be fully understood. Hence, we investigated the potential role of reactive oxygen species (ROS) and dynamin-related protein 1 (DRP1) in PQ-induced mitophagy, aiming to elaborate on possible molecular mechanisms involved in PQ-triggered neurotoxicity. Our results showed that ROS were increased, mitochondrial membrane potential was decreased at 100, 200, and 300 μM PQ concentrations, and autophagy pathways were activated at a concentration of 100 μM in neuronal cells. In addition, excessive mitophagy was observed in neurons exposed to 300 μM PQ for 24 h. Then, ROS-mediated mitochondrial fission was found to contribute to PQ-induced excessive mitophagy. Moreover, all aforementioned changes were significantly ameliorated by mdivi-1. Thus, our findings provide a novel neurotoxic mechanism and reveal the DRP1-mitochondrial fission pathway as a potential target for treatments of PQ-induced excessive mitophagy, serving as an alternative target for the prevention and treatment of Parkinson’s disease. Because harmful substances are transmitted and enriched in the food chain, the toxic effect of environmental paraquat is nonnegligible, and more investigations are needed.

Tetrachlorobenzoquinone (TCBQ) is a common metabolite of persistent organic pollutants pentachlorophenol (PCP) and hexachlorobenzene (HCB). Current reports on the toxicity of TCBQmainly focused on its reproductive toxicity, neurotoxicity, carcinogenicity and cardiovascular toxicity. However, the possible immunotoxicity of TCBQ remains unclear. The release of neutrophil extracellular traps (NETs) is a recently discovered immune response mechanism, however, excess NETs play a pathogenic role in various immune diseases. In an attempt to address concerns regarding the immunotoxicity of TCBQ, we adopted primary mouse neutrophils as the research object, explored the influence of TCBQ on the formation of NETs. The results showed that TCBQ could induce NETs rapidly in a reactive oxygen species (ROS)-dependent manner. Moreover, TCBQ promoted the phosphorylation of c-Jun N-terminal kinase (JNK) mitogen activated protein kinase (MAPK), but not p38 or extracellular signal related kinase (ERK) in neutrophils. Mechanistically, JNK activation enhanced the expression of NADPH oxidase enzyme 2 (NOX2), which further accelerated the generation of ROS and thus amplified the formation of NETs. The pharmacologic blockage of JNK or NOX2 effectively ameliorated TCBQ-induced ROS and NETs, implying that ROS-JNK-NOX2 positive feedback loop was involved in TCBQ-induced NETs. In conclusion, we speculated that targeting NETs formation would be a promising therapeutic strategy in modulating the immunotoxicity of TCBQ.