Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Current issue
Displaying 1-5 of 5 articles from this issue
Original Article
  • Tomohiro Ito, Xian-Yang Qin, Yoshika Kurokawa, Yang Zeng, Satoshi Otsu ...
    2024 Volume 11 Issue 3 Pages 87-98
    Published: 2024
    Released on J-STAGE: June 11, 2024
    JOURNAL FREE ACCESS
    Supplementary material

    Many epidemiological and animal exposure studies have suggested that exposure to environmental substances is a major risk factor for developmental neurotoxicity (DNT), such as in autism, and is related to the increasing relevance of neurodevelopmental disorders. Recent efforts have led to the development of various in vitro approaches that use cell lines and pluripotent stem cells to assess numerous environmental substances. In this study, we developed a method for assessing DNT using a mouse embryonic stem (mES) cell model that focuses on differentiation into neuronal cells (neural cells and astrocytes). Using this model system, we found that six insecticides inhibited the differentiation of neural precursor cells into astrocytes. Our data indicated that the effects of insecticides on glial differentiation were more sensitive than those of several DNT markers reported in previous studies. This mES cell model can make a quick assessment of DNT potential and may be a useful tool for screening substances with potential to induce DNT.

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Original Article
  • Nguyen Thi Quynh, Huiho Jeong, Ahmed Elwaleed, Yasuhiro Ishibashi, Koj ...
    2024 Volume 11 Issue 3 Pages 99-108
    Published: 2024
    Released on J-STAGE: June 11, 2024
    JOURNAL FREE ACCESS

    Mercury (Hg) accumulation in rice is a health concern due to the consumption of rice as the staple food. This study evaluated the mercury contamination in rice plants, which are typical foods cultivated in the Red River Delta. During the harvest season, rice samples were collected and separated into husk and brown rice, together with polished white rice and bran rice from mill shop. For brown rice, the Hg concentration ranges from 7.18 ± 0.73 to 16.32 ± 2.57 µg/kg. Additionally, brown rice samples near landfill or highway tend to have higher Hg concentrations than sites farther away. Hazard quotient (HQ) was used to measure the health risk of Hg in this study. HQ values of male and female all were less than one, indicating that consuming rice from Nam Son and Bac Son might not cause potential human health risk of Hg exposure.

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Original Article
  • Ryoya Takizawa, Akihiko Ikegami, Cai Zong, Syun Nemoto, Yuki Kitamura, ...
    2024 Volume 11 Issue 3 Pages 109-121
    Published: 2024
    Released on J-STAGE: June 11, 2024
    JOURNAL FREE ACCESS

    Nanoparticles (NPs) are used in a variety of fields, including industry, medicine, and food production. Predicting the potential toxicity and biological effects of NPs is challenging due to the influence of their physicochemical properties, such as particle shape and coating constituents. This study investigated the pulmonary effects of differently coated titanium dioxide (TiO2) NPs in wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2) null mice. C57BL6/J wild-type and Nrf2 null mice were exposed to uncoated TiO2 NPs, or NPs coated with either hydroxide aluminum, or with aluminum hydroxide/stearic acid. After a two-week exposure period, no significant changes were observed in lung weight, cell counts of bronchoalveolar lavage fluid, mRNA levels of proinflammatory cytokines, and antioxidant gene expression in either mouse strain. In addition, human lung carcinoma A549 cells exposed to three types of TiO2 NPs showed no significant changes in cell viability, cytotoxicity, or intracellular reactive oxygen species production. These findings suggest that the toxicity of the TiO2 NPs, regardless of surface modification, is minimal to the respiratory system of mice and human alveolar epithelial cells.

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Minireview
  • Nozomi Fujisawa
    2024 Volume 11 Issue 3 Pages 123-130
    Published: 2024
    Released on J-STAGE: June 19, 2024
    JOURNAL FREE ACCESS

    In non-clinical toxicity studies for drug development, reduced food intake in experimental animals can lead to fluctuations in various toxicological parameters, complicating the distinction between drug toxicity and secondary effects of reduced food intake. This review examines the parameters that change due to food restriction in rats, dogs, and monkeys, and discusses the presumed mechanisms behind each parameter change. The parameters include standard toxicological evaluation parameters, such as body weight, blood chemistry, hematology, urinalysis, bone marrow cell analysis, organ weight, and histopathology. This review also highlights the differences in parameter changes across animal species and food restriction conditions, providing crucial insights for improving the quality of non-clinical toxicity studies and enhancing human translatability. The review underscores the need for a comprehensive analysis of these parameters to understand animal nutritional status within toxicity studies. This information can improve the reliability of toxicity evaluations.

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Toxicomics Report
  • Kensuke Sato, Ryota Nakano, Yoshitaka Yamazaki, Hikaru Isobe, Yun-Gi K ...
    2024 Volume 11 Issue 3 Pages 131-139
    Published: 2024
    Released on J-STAGE: June 19, 2024
    JOURNAL FREE ACCESS

    Methylmercury (MeHg), a potent neurotoxin, poses substantial risks to prenatal brain development by crossing the placental barrier. In our daily lives, we are exposed to various environmental metals simultaneously with MeHg. Therefore, the combined exposure effects of these metals and MeHg should be investigated. Hence, this study examined the combined fetal exposure effects of MeHg and copper (Cu), an essential element. Gene expression changes in the fetal brains of mice exposed to MeHg, Cu, or both were examined through RNA-seq analysis. Our results showed that the number of variable genes exposed to combined MeHg and Cu increased compared with that in single exposure. Most of them were gene variations specific to combined exposure. Gene Ontology biological process analysis revealed the amplified effects on GABAergic interneurons in the cerebral cortex under combined exposure. IPA pathway analysis indicated considerable variations in pathways related to oxidative stress, neuronal development, and energy metabolism, including the activation of NRF2-mediated oxidative stress response and the suppression of mitochondrial fatty acid beta-oxidation. These findings highlighted the complexity and enhanced risks of combined MeHg and Cu exposure. Therefore, neurodevelopmental effects were more severe and multifaceted than those caused by individual exposures. This research highlighted the importance of understanding the mechanisms of the combined exposure effects of MeHg.

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