Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
  • Yukie Kuroda, Atsuko Miyajima, Kazue Sakemi-Hoshikawa, Makoto Usami, K ...
    2020 年 7 巻 6 号 p. 249-252
    発行日: 2020年
    公開日: 2020/08/26
    ジャーナル フリー

    2-Mercaptobenzimidazole (MBI) and its methyl derivatives 4-methyl-MBI (4-MeMBI), 5-methyl-MBI (5-MeMBI), and 4(or 5)-methyl-MBI (4(5)-MeMBI) are widely applied industrial agents with substantial thyrotoxicity and hepatotoxicity detected in rats in vivo. Here, we examined the in vitro cytotoxicity of MBI and its derivates in cultured SIRC rabbit corneal cells. SIRC cells were cultured in the presence of the test chemicals for 72 hr, and cell viability was determined by estimating the number of cells using a crystal violet staining assay. The median lethal concentration (LC50) was calculated for each of the chemicals. The methyl derivatives showed higher cytotoxicity than MBI, which is in contrast to previous in vivo findings demonstrating higher thyrotoxicity and hepatotoxicity of MBI compared to its derivates. According to the LC50 values, the ranking of the tested agents in terms of cytotoxicity was 5-MeMBI (761.5 µM) ≥ 4-MeMBI (796.3 µM) ≥ 4(5)-MeMBI (822.9 µM) > MBI (1002.9 µM). The present results suggest that the lower thyrotoxicity and hepatotoxicity of methyl derivatives of MBI is related to their faster detoxification in vivo, because SIRC cells are considered to have lower drug-metabolizing activity than hepatic cells.

  • Masami Ishido, Eiko Shimaya
    2020 年 7 巻 6 号 p. 253-257
    発行日: 2020年
    公開日: 2020/10/21
    ジャーナル フリー

    There are both advantages and disadvantages in the application of electromagnetic fields (EMF) for health: the former is deep brain stimulation for neurodegenerative disease in medicine and the latter is the possible association with a tumor. In this study, we examined the effect of EMF (50 Hz; 100 μT) on rat neural stem cells in vitro. During handling with culture cells, there are two phases of the state of neural stem cells isolated from rat brains; one phase is a cellular suspension in the medium (no anchorage), and another phase is anchorage to the bottom of the culture dishes. The effect of EMF on neural stem cells in vitro was dependent on these cellular phases. Upon anchorages, the cultured neural stem cells migrated along the radial axis, and exposure of these migratory neural stem cells to EMF (50 Hz; 100 μT) facilitates the migration and incorporation of BrdU 1.3~1.4 folds. However, these effects of EMF were not seen once the cellular suspension (no anchorage) was exposed. Even when the neural stem cells fully migrated, there were no effects of EMF on the retinoic acid-induced differentiation. Thus, there is a cell phase sensitive to EMF in the cultured neural stem cells.

Original Article
  • Akira Kawashima, Kaoru Inoue, Yoshiro Yoshizaki, Kazuo Ushida, Kaoru K ...
    2020 年 7 巻 6 号 p. 259-279
    発行日: 2020年
    公開日: 2020/10/23
    ジャーナル フリー

    3-Methylpentane, isooctane, and isononane are acyclic branched saturated hydrocarbons with carbon numbers C6, C8, and C9, respectively. To assess human risk, we conducted a combined repeated-dose and reproductive/developmental oral toxicity studies in rats. [Organization for Economic Co-operation and Development (OECD) Test Guideline 422]. Each hydrocarbon was administered by gavage to rats at three doses (plus a control group). All three chemicals targeted the liver and kidney. An increase in liver weight without hepatic injury was observed as the adaptive response to the chemical treatments. Males treated by each chemical showed α2u-globulin nephropathy, which is a rat-specific finding that bears no human relevance. Reproduction/developmental toxicity parameters showed no treatment-related effects in parents or offspring at any dose for the three chemicals, except for the retardation of offspring bodyweight development which may be a secondary effect of a maternal systemic condition or direct effect on offspring in isononane. No observed adverse effect levels (NOAELs) of repeated toxicity in either sex were determined to be 300 mg/kg/day for 3-methylpentane, 100 mg/kg/day for isooctane, and 250 mg/kg/day for isononane. NOAELs of reproductive/developmental toxicity in parents and offspring were determined to be 1000 mg/kg/day for 3-methylpentane, and 300 mg/kg/day for isooctane. For isononane, NOAELs were determined to be 1000 mg/kg/day for reproduction, and 250 mg/kg/day for offspring development. These results provide new toxicological information and support the category assessment of published reports that evaluate the acyclic branched saturated hydrocarbons as low-toxicity substances.