Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Volume 10, Issue 4
Displaying 1-4 of 4 articles from this issue
Original Article
  • Nahida Sultana, Katsumi Fukamachi, Dipankar Chandra Roy, Jiegou Xu, Hi ...
    2023 Volume 10 Issue 4 Pages 137-141
    Published: 2023
    Released on J-STAGE: June 14, 2023

    Some types of multiwalled carbon nanotube (MWCNT) are similar to asbestos in length and diameter. When these fibers are introduced into the respiratory tract, MWCNTs can induce pulmonary lesions including inflammation, fibrosis, and hyperplasia. By using an intrapulmonary spraying method, we demonstrate that MWCNT causes lung cancer in a 2-year experimental protocol (Suzui et al., 2016). In samples of the 5 histologically diagnosed archival lung cancer tissues and 4 control normal lung tissues, we examined the mRNA expression level of specific cytokines such as CCL4, IL6, and CXCL2. These cytokines were chosen for the analysis since their mRNA expression levels are upregulated in MWCNT-treating macrophages (Sultana et al., 2023). The level of expression of CCL4 markedly decreased in adenocarcinoma compared to that of the control normal lung tissue. In several adenocarcinoma samples, the level of expression of IL6/CXCL2 was higher than that of the control normal lung tissue. In the granuloma sample, the level of IL6 was higher than that of the control normal lung tissue and the level of CCL4/CXCL2 was lower than that of the control normal lung tissue. Taken together, histology specific expression profile of these cytokines may provide additional insights into lung tumorigenesis induced by MWCNT.

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Data Report
  • Chin Piow Wong, Yukiko Kobayashi, Jinwei Yang
    2023 Volume 10 Issue 4 Pages 143-156
    Published: 2023
    Released on J-STAGE: June 23, 2023

    The erroneous assumption that herbal products is generally safe for consumption, is a major factor leading to the increased of herb-induced liver injury (HILI). Even though Laurus nobilis or laurel is a commonly used spice, the safety aspect for its consumption is under-studied. To bridge this gap of knowledge, the mutagenicity, acute toxicity, and subacute toxicity of LAURESH®, which is a standardized laurel leaf extract were evaluated. Mutagenicity study using two S. typhimurium strains, TA100 and TA98 indicated that LAURESH® does not cause base substitution and frameshift mutation, thus suggesting that LAURESH® is non-mutagenic. While acute oral toxicity on mice established the LD50 at no less than 2,000 mg/kg of body weight, and a 28-day subacute toxicity test on rat revealed the NOAEL to be 1,000 mg/kg/day. Furthermore, blood chemistry, urinalysis, necropsy, and histopathological data from subacute toxicity study on rats does not show adverse event that could be attributed to LAURESH®, thus indicating that LAURESH® is unlikely to cause HILI. Taken together, the findings from this study and previous clinical study on LAURESH®, in combination with the historic use of laurel and previous toxicity studies conducted on laurel leaves extract, strongly suggest that LAURESH® is safe for human consumption.

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Original Article
  • Megumi Sakata, Tomoaki Araki, Masayuki Tomohiro
    2023 Volume 10 Issue 4 Pages 157-167
    Published: 2023
    Released on J-STAGE: July 04, 2023

    Intravitreal (IVT) injections are the current method for retinal drug delivery and have been widely used in humans, although it is well known that IVT injections often cause an increase in intraocular pressure (IOP) that closely relates to the injection volume. Because of the anatomical and physiological similarities of the monkey and human eye, cynomolgus monkeys are often used for preclinical studies on new treatments using large molecules or gene therapy requiring IVT application. However, there is only limited information on the maximal dosing volume for IVT injections in cynomolgus monkeys. To determine an appropriate maximal dosing volume for IVT injections, comprehensive ocular examinations were conducted in IVT-injected eyes of cynomolgus monkeys. Up to a dosing volume of 150 µL/eye by IVT injection, there were no IVT injection-related ocular findings in pupillary light reflex gross observations, slit lamp biomicroscopic and indirect ophthalmoscopic and fundus autofluorescent examinations, intraocular pressure, optical coherence tomography of the anterior and posterior segments of the eye, axial length measurement, electroretinogram waveforms, or histopathological examinations of treated eyes. However, leakage of the dosing solution from an eye was observed at 150 µL/eye, indicating a technical limitation for the maximal applicable volume. In addition, recovery from IOP elevation immediately after injection of 150 µL/eye was slower than after injections of 50 or 100 µL/eye. Therefore, we recommend a maximal volume of 100 µL/eye for IVT injections in cynomolgus monkeys.

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Original Article
  • Takayasu Moroki, Fumika Akizawa, Satoshi Kondo, Sakura Fujiwara, Tsuyo ...
    2023 Volume 10 Issue 4 Pages 169-178
    Published: 2023
    Released on J-STAGE: July 11, 2023

    In toxicity studies, it is important to select a vehicle that does not affect the toxicity assessment of the test substance. To obtain toxicity information on corn oil as a Vehicle for subcutaneous toxicity studies of non-aqueous test substances, Crl:CD (SD) rats (6 animals/sex/group) were repeatedly dosed with corn oil at 0 (negative control; saline), 1, 2 and 5 mL/kg/day for 4 weeks. High body weight due to retention of the administered substance were found in corn oil groups in both sexes at 2 mL/kg/day or higher. Some relative organ weights at 2 mL/kg/day or higher were decreased due to high body weight or body weight gain. Subcutaneous retention of the administered substance found in all corn oil-treated groups at necropsy was observed on histopathological analysis as accumulation of the administered substance and granulation tissue. Accumulation of the administered substance in inguinal skin, the axillary lymph node, and alveolus of the lung and bronchus was observed. Multiple white nodules in the abdominal cavity and liver observed in a female at 5 mL/kg/day at necropsy were considered to be related to lipogranuloma at the peritoneum and hepatic capsule. In hematology, RBC was lower in females at the 5 mL/kg/day than in the control group.. In conclusion, since the effects of corn oil administration were found in groups at all volumes, it is necessary to take into account that corn oil induces these changes when used as a vehicle of a test substance in toxicity studies.

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