Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
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Original Article
  • Takashi Yamada, Tomoko Kawamura, Taeko Maruyama, Masayuki Kurimoto, Hi ...
    2021 Volume 8 Issue 7 Pages 195-204
    Published: 2021
    Released: November 16, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Releasing human pharmaceuticals to the environment is an emerging ecotoxicological concern. In this study, we examine the feasibility of evaluating the algal chronic toxicity of human pharmaceuticals using quantitative structure–activity relationship (QSAR) models and a category approach. We constructed an ecotoxicology database of human pharmaceuticals using publicly available information, such as regulatory agency reports and scientific papers. We created an algal chronic toxicity dataset using this database, and predicted the No Observed Effect Concentrations (NOEC) of human pharmaceuticals using ECOlogical Structure-Activity Relationship (ECOSAR) and KAshinhou Tool for Ecotoxicity (KATE) QSAR models. Almost half of query substances were applicable to the QSAR models, and the feasibility was confirmed with high concordant predictions—predicted/measured ratios were in the range of 0.01–100 in 92.9% and 79.1% of applicable substances in ECOSAR and KATE, respectively—and false predictions (predicted/measured ratios > 100) that could lead to significant underestimation of toxicity were rarely observed. Two case studies of diphenhydramine and lamotrigine demonstrated that detailed evaluation of target and reference substances in the corresponding chemical class could increase the reliability and accuracy of prediction results of KATE. Grouping of substances based on pharmacology revealed some category classes with a toxicological concern. Finally, a workflow model to assess algal toxicity of human pharmaceuticals was proposed based on these evaluations including QSAR predictions and category approach.

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Letter
  • Atsuko Miyajima, Tsuyoshi Kawakami, Kaoru Komoriya, Reiko Kato, Makoto ...
    2021 Volume 8 Issue 7 Pages 205-213
    Published: 2021
    Released: November 25, 2021
    JOURNAL FREE ACCESS

    Two zinc oxide nanoparticles (ZnO NPs) with different physicochemical properties (ZnO(α) and ZnO(Σ)) were examined in THP-1 cells to investigate their effects on cellular immunomodulation and cytotoxicity. THP-1 cells were cultured in the presence of ZnO(α) or ZnO(Σ) for 48 hr, and the expression of proinflammatory cytokines and immune cell surface antigens was examined. ZnO(α) and ZnO(Σ) reduced cell viability in a concentration- and time-dependent manner, with the latter being more potent. ZnO(α) and ZnO(Σ) increased the expression of CD54, IL-8, and TNF-α to the same extent between 24 and 48 hr. While ZnO(Σ) was more potent at effective concentrations, this potency was comparable between ZnO(α) and ZnO(Σ) when normalized to their cytotoxic concentrations (LC50, LC25, or LC5). It was considered that there was a potency shift that is associated with cytotoxicity and physicochemical properties, in immunomodulatory activities in THP-1 cells between ZnO NPs.

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Letter
  • Seiko Hashiguchi, Aki Miyauchi, Keiji Komemoto, Tomoyuki Ueda, Kenji T ...
    2021 Volume 8 Issue 7 Pages 215-220
    Published: 2021
    Released: November 25, 2021
    JOURNAL FREE ACCESS

    To evaluate the effects of multi-walled carbon nanotubes (MWCNT) on a host immune system, we assayed them using a murine model of respiratory syncytial virus (RSV) infection. MWCNT suspended in solution were intranasally administered to mice on days 1, 3, and 5 before RSV infection. On day 5 post-infection, the levels of representative inflammatory markers (interferon-γ, chemokines CCL3 and CCL5) in bronchoalveolar lavage fluid (BALF) were significantly increased in RSV-infected mice due to MWCNT exposure compared to the control. A histopathological analysis confirmed the exacerbation of the pneumonia. However, significant histopathological changes were not observed in mock-infected mice in this study. Some alveolar macrophages engulfing the MWCNT aggregates were localized in the inflammatory cells in the lung tissues, but RSV-positive cells immunohistopathologically stained with an anti-RSV antibody were observed apart from those cells. Thus, intranasal treatment with MWCNT should affect the pulmonary immune response against RSV, exacerbating RSV infection in mice.

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