Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Volume 6, Issue 4
Displaying 1-3 of 3 articles from this issue
Toxicomics Report
  • Hitomi Fujishiro, Seiichiro Himeno
    2019 Volume 6 Issue 4 Pages 117-123
    Published: 2019
    Released on J-STAGE: May 14, 2019

    Kidney proximal tubules are composed of S1, S2, and S3 segments having different properties of excretion and substance reabsorption. Since renal toxicants such as cadmium and cisplatin cause segment-specific toxicity, it is important to examine the segment-specific transport and detoxification systems of renal toxicants. Here, we investigated the gene expression profiles of immortalized S1, S2, and S3 cells derived from each segment of mouse kidney proximal tubules. Microarray analyses showed distinct expression of various genes in each cell line. We compared the expression levels of selected genes related to the transport and detoxification of renal toxicants. Some genes showed segment-specific expression patterns similar to those observed in in vivo studies. The gene expression profiles of each cell line shown in this study will provide a foundation for the future utilization of immortalized S1, S2, and S3 cells for toxicity screenings as well as for the elucidation of renal toxicity mechanisms.

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Original Article
  • Mariko Matsumoto, Mutsuko Hirata-Koizumi, Tomoko Kawamura, Sawako Saku ...
    2019 Volume 6 Issue 4 Pages 125-136
    Published: 2019
    Released on J-STAGE: May 16, 2019

    The benchmark dose (BMD) approach is one of the important techniques in dose-response assessment for the risk assessment of chemicals and adapted by various international organizations. We investigated the appropriateness of the statistical parameters and model selection criteria for BMD lower bound (BMDL) estimation by BMD software (BMDS) (developed by the US Environmental Protection Agency) and PROAST (developed by the National Institute for Public Health and the Environment of the Netherlands). Publicly available repeated-dose toxicity study data (226 dichotomous datasets and 151 continuous datasets) were used for the investigation. Our findings were applied to establish BMD technical guidance for BMDS for the evaluation of various endpoints in repeated-dose toxicity studies. Under the Japan Chemical Substance Control Law (CSCL), the DRA-BMDS guidance (i.e., Division of Risk Assessment-BMDS guidance) is used for the evaluation of a “Priority Assessment Chemical Substance.” Namely, selecting of an extra risk of 10% (dichotomous data) or a level change of 1SD (continuous data) as a default benchmark response. Running all the models without or with parameter constraints. Selecting the model that calculated the lowest BMDL but excluding the one that estimated a BMD/BMDL ratio ≥ 10 or lowest dose/BMDL ratio ≥ 10. We believe that the DRA-BMDS guidance can assist risk assessors in the selection of the BMD model.

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  • Koki Sugimoto, Ryota Hosomi, Kenji Fukunaga, Takaki Shimono, Seiji Kan ...
    2019 Volume 6 Issue 4 Pages 137-143
    Published: 2019
    Released on J-STAGE: June 13, 2019

    Discarded scallop internal organs, especially the hepatopancreas, are rich in n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. However, they have not been utilized because of their contamination with toxic substances, such as cadmium (Cd), and the occurrence of diarrheic shellfish toxins (DST). We have successfully prepared a high-quality scallop oil (SCO) from the internal organs of the Japanese giant scallop (Patinopecten yessoensis), including the hepatopancreas without Cd and DST. These pollutants were removed by liquid-liquid partitioning followed by adsorption to active carbon of fine particle size with high pore surface volume. In this study, we prepared SCO from scallop internal organs obtained from two different processing areas (Mutsu and Uchiura bays, Japan), and referred to them as SCO-M and SCO-U, respectively. Genotoxicity of SCO-M and SCO-U was evaluated by the in vitro bacterial reverse mutation test (Ames test) and in vivo micronucleus test in accordance with the Organisation for Economic Co-operation and Development guidelines. SCO-M and SCO-U showed negative results in the Ames test in the presence or absence of metabolic activation with S9 mix. In addition, no genotoxic effects of SCO-M and SCO-U were observed at all tested doses in the micronucleus test. Based on the results of the present study, it can be concluded that SCO-M and SCO-U are safe products in terms of genotoxicity under these experimental conditions.

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