There is growing concern that sprayed neonicotinoid pesticides (neonics) persist in mixed forms in the environmental soil and water systems, and these concerns stem from reports of increase in both the detection frequency and concentration of these pollutants. To confirm the toxic effects of neonics, we conducted toxicity tests on two neonics, clothianidin (CLO) and imidacloprid (IMD), in embryos of zebrafish. Toxicity tests were performed with two different types of mixtures: potential mixture compounds and realistic mixture compounds. Potential mixtures of CLO and IMD exhibited synergistic effects, in a dose-dependent manner, in zebrafish embryonic toxicity. Realistic mixture toxicity tests that are reflecting the toxic effects of mixture in the aquatic environment were conducted with zebrafish embryos. The toxicity of the CLO and IMD mixture at environmentally-relevant concentrations was confirmed by the alteration of the transcriptional levels of target genes, such as cell damage linked to oxidative stress response and thyroid hormone synthesis related to zebrafish embryonic development. Consequently, the findings of this study can be considered a strategy for examining mixture toxicity in the range of detected environmental concentrations. In particular, our results will be useful in explaining the mode of toxic action of chemical mixtures following short-term exposure. Finally, the toxicity information of CLO and IMD mixtures will be applied for the agricultural environment, as a part of chemical regulation guideline for the use and production of pesticides.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is commonly used in rubber compounds as antioxidants to protect against degradation from heat, oxygen, and ozone exposure. This practice extends the lifespan of rubber products, including tires, by preventing cracking, aging, and deterioration. However, the environmental consequences of waste generated during rubber product use, particularly the formation of 6PPD-quinone (6PPD-Q) through the reaction of 6PPD with ozone, have raised significant concerns due to their detrimental effects on ecosystems. Extensive research has revealed the widespread occurrence of 6PPD and its derivate 6PPDQ in various environmental compartments, including air, water, and soil. The emerging substance of 6PPD-Q has been shown to pose acute mortality and long-term hazards to aquatic and terrestrial organisms at concentrations below environmentally relevant levels. Studies have demonstrated toxic effects of 6PPD-Q on a range of organisms, including zebrafish, nematodes, and mammals. These effects include neurobehavioral changes, reproductive dysfunction, and digestive damage through various exposure pathways. Mechanistic insights suggest that mitochondrial stress, DNA adduct formation, and disruption of lipid metabolism contribute to the toxicity induced by 6PPD-Q. Recent findings of 6PPD-Q in human samples, such as blood, urine, and cerebrospinal fluid, underscore the importance of further research on the public health and toxicological implications of these compounds. The distribution, fate, biological effects, and underlying mechanisms of 6PPD-Q in the environment highlight the urgent need for additional research to understand and address the environmental and health impacts of these compounds.

Phenols, ubiquitous environmental contaminants found in water, soil, and air, pose risks to organisms even at minimal concentrations, and many are classified as hazardous pollutants. Skin pigmentation is a natural shield against ultraviolet-induced DNA damage and oxidative stress, pivotal in reducing skin cancer incidences. Studies on B16F10 melanoma cells and zebrafish offer valuable insights into potential therapeutic avenues for melanoma in the context of phenol exposure. Upon phenol treatment, there was a marked decrease in melanin content and melanogenesis-associated protein expression, such as tyrosinase and the microphthalmia-associated transcription factor (MITF) in these melanoma cells. Additionally, phenols led to diminished p38 phosphorylation, amplified extracellular signal-regulated kinase (ERK) phosphorylation, and curtailed melanin expression in zebrafish. These observations underscore the detrimental impact of phenols on melanogenesis and propose a mechanism of action centered on the ERK/p38 signaling pathway. Consequently, our data spotlight the adverse effects of phenols on melanogenesis.

Butyl benzyl phthalate (BBP), a widely used class of plasticizers, has caused considerable concerns due to its widespread detection in various environmental media. However, the potential impact of BBP on the brain and its underlying molecular mechanisms remain poorly understood. In this study, adult zebrafish (Danio rerio) were exposed to 0, 5, 50, and 500 mu g/L BBP for 28 days. Elevated levels of both reactive oxygen species and 8-hydroxydeoxyguanosine were observed, indicating the occurrence of oxidative stress and DNA damage. Furthermore, exposure to BBP resulted in neurotoxicity, apoptosis, and histopathological damage within the zebrafish brain. Transcriptome analysis further revealed that Gene Ontology terms associated with muscle contraction were specifically expressed in the brain after BBP exposure. In addition, BBP altered the transcriptome profile of the brain, with 293 genes induced and 511 genes repressed. Kyoto Encyclopedia of Genes and Genomes analysis highlighted the adverse effects of BBP on the complement and coagulation cascades and two cardiomyopathyrelated pathways. Taken together, our results revealed that BBP resulted in brain oxidative stress, histological damage, and transcriptome alterations. These findings have the potential to offer novel insights into the adverse outcome pathways of key events in the brain.