The Journal of Toxicological Sciences

Our medical research library holds 9 studies published in The Journal of Toxicological Sciences (2008–2023). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 8 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Doku Sayō Kenkyūkai
• Published: 1976 to the present, Japan
• Language: English, Japanese
• ISSN: 0388-1350 (print), 1880-3989 (electronic)
• Its record in the NLM Catalog

2020s

• Effects of inhalation of multi-walled carbon nanotube (MWCNT) on respiratory syncytial virus (RSV) infection in mice. A. Miyauchi, T. Akashi, S. Yokota, et al. 2023;48(7):411-420. PubMed · Publisher

  Abstract

  Multi-walled carbon nanotubes (MWCNTs), a kind of nanomaterial, are widely used in battery electrodes and composite materials, but the adverse effects associated with their accumulation in the living body have not been sufficiently investigated. MWCNTs are a fibrous material with molecules similar to asbestos fibers, and there are concerns about its effects on the respiratory system. In this study, we conducted a risk assessment by exposing mice using a previously developed nanomaterial inhalation exposure method. We quantified the exposure in the lungs by a lung burden test, evaluated the deterioration due to pneumonia using respiratory syncytial virus (RSV) infection, and measured inflammatory cytokines in bronchoalveolar lavage fluid (BALF). As a result, in the lung burden test, the amount of MWCNT in the lung increased according to the inhalation dose. In the RSV infection experiment, CCL3, CCL5, and TGF-β, which are indicators of inflammation and lung fibrosis, were elevated in the MWCNT-exposed group. Histological examination revealed cells phagocytosing MWCNT fibers. These phagocytic cells were also seen during the recovery period from RSV infection. The present study found that MWCNT remained in the lungs for about a month or more, suggesting that the fibers may continue to exert immunological effects on the respiratory system. Furthermore, the inhalation exposure method enabled the exposure of nanomaterials to the entire lung lobe, allowing a more detailed evaluation of the effects on the respiratory system.

2010s

• Teratogenicity of asbestos in mice. T. Fujitani, M. Hojo, A. Inomata, et al. 2014;39(2):363-70. PubMed · Publisher

  Abstract

  Possible teratogenicity of 3 different asbestos (crocidolite, chrysotile and amosite) was assessed in CD1(ICR) mice. Dams on day 9 of gestation were given a single intraperitoneal administration at dose of 40 mg/kg body weight of asbestos suspended in 2% sodium carboxymethyl cellulose solution in phosphate buffered saline, while dams in the control group were given vehicle (10 ml/kg body weight). Dams and fetuses were examined on day 18 of gestation. To compare with the control group, the mean percentage of live fetuses in implantations in the group given crocidolite and the incidence of dams with early dead fetuses in the groups given chrysotile or amosite were increased. While no external or skeletal malformation was observed in the control group, the incidence of external malformation (mainly reduction deformity of limb) in the group given amosite, and the incidences of skeletal malformation (mainly fusion of vertebrae) in the all dosed groups were significantly increased. The result indicated that asbestos (crocidolite, chrysotile and amosite) have fetotoxicity and teratogenicity in mice.

• Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice. A. Yamaguchi, T. Fujitani, K. Ohyama, et al. 2012;37(1):177-89. PubMed · Publisher

  Abstract

  Possible effects of multi-wall carbon nanotubes (MWCNTs) on immune and inflammatory responses were examined in mice. Female ICR mice were given a single intraperitoneal administration (2 mg/kg body weight) of either MWCNTs, carbon black (CB), or crocidolite (blue asbestos) and controls received a vehicle of 2% sodium carboxymethyl cellulose (CMC Na). In the peritoneal cavity of MWCNT-administered mice, the liver had changed to a rounded shape and fibrous adhesions were seen on internal organs. Peritoneal cells overexpressed mRNA for genes of T helper (Th)2 cytokines (interleukin [IL]-4, IL-5, and IL-13), Th17 cytokine (IL-17), pro-inflammatory cytokines/chemokines (IL-1β, IL-33, tumor necrosis factor α, and monocyte chemotactic protein-1), and myeloid differentiation factor 88 for at least 2 weeks after the administration of MWCNTs, while those of Th1 cytokine genes (IL-2 and interferon γ) were overexpressed several weeks later and expression levels remained high up to 20 weeks. In MWCNT-treated mice, the numbers of leukocytes, monocytes, and granulocytes in the peripheral blood and the expression of the leukocyte adhesion molecules, cluster of differentiation (CD)49d and CD54, on granulocytes were increased 1 week after administration and remained high up to week 20. Production of ovalbumin-specific IgM and IgG(1) was enhanced by MWCNTs. These changes were not observed after CB or crocidolite administration. Thus, this study showed that MWCNTs exhibited sustained stimulating effects on immune and inflammatory responses, unlike the other mineral fibers with structural similarities.

• Evaluation of hazardousness of refractory fibers by cell magnetometry. Y. Kudo, M. Kotani, Y. Aizawa. 2010;35(6):807-15. PubMed · Publisher

  Abstract

  This study was carried out to assess the cytotoxicity of three kinds of refractory fibers (RFs), RF1, RF2, and RF3, by cell magnetometry, lactate dehydrogenase (LDH) assay and morphological observation by scanning electron microscopy, using a mouse-derived cultured cell line, RAW264.7. As an indicator for cell magnetometry, Fe(3)O(4) was added to RAW264.7 cells. RF1, RF2 and RF3 were each added to an aliquot of this solution to make final concentrations of 250, 500 and 1,000 µg/ml in the experimental group. Phosphate buffered solution was added to make the control solution (n = 6). After culturing for 48 hr, the solution was magnetized from outside using a cell magnetometric apparatus, and the remnant magnetic field was measured for 20 min postmagnetization. In cell magnetometry, a significant delay of relaxation compared to that of the control was observed. In the LDH assay, LDH release into the culture medium was observed by addition of RFs. Furthermore, a quantity-dependent relationship was found between the quantity of RF added and the cytotoxicity in cell magnetometry and LDH assay. Morphological examination revealed incomplete phagocytosis of fibers and a decrease of microvilli in the experimental groups. These results suggest that RFs are cytotoxic to RAW264.7 cells, showing concentration-dependent cytotoxicity, and have a possible risk of cytotoxicity similar to that of asbestos. Further studies by pulmonary magnetometry are necessary to assess the hazardousness of RFs.

2000s

• Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. Y. Sakamoto, D. Nakae, N. Fukumori, et al. 2009;34(1):65-76. PubMed · Publisher

  Abstract

  The present study assessed a carcinogenic hazard of multi-wall carbon nanotube (MWCNT) in intact (not genetically modified) rodents. MWCNT (1 mg/kg body weight, 7 animals), crocidolite (2 mg/kg body weight, 10 animals) or vehicle (2% carboxymethyl cellulose, 5 animals) was administered to male Fischer 344 rats (12 weeks old) by a single intrascrotal injection. Rats were autopsied immediately after death, when becoming moribund or at the end of the maximal observation period scheduled to be 52 weeks. After 37-40 weeks, however, 6 MWCNT-treated animals died or became moribund due to intraperitoneally disseminated mesothelioma (6/7, 85.7%) with bloody ascites. Peritoneal mesothelium was generally hypertrophic, and numerous nodular or papillary lesions of mesothelioma and mesothelial hyperplasia were developed. While mesothelioid cells were predominant in relatively early stage tumors, advanced stage mesotheliomas were constituted by 2 portions occupied by mesothelioid cells on the surface and spindle-shaped sarcomatous cells in the depth. In the latter, the histological transition was apparently observed between these 2 portions. Mesotheliomas were invasive to adjacent organs and tissues, and frequently metastasized into the pleura. Only 1 rat survived for 52 weeks in the MWCNT-treated group, and similar findings except mesothelioma were observed. All 10 crocidolite-treated and 5 vehicle-treated rats survived for 52 weeks without any particular changes except deposition of asbestos in the former case. It is thus indicated that MWCNT possesses carcinogenicity causing mesothelioma at a high rate in intact male rats under the present experimental conditions. The present data identifies a carcinogenic hazard of MWCNT and will serve as one of the indispensable evidences to be used for the risk assessment crucial for not only protection and improvement of human health and welfare, but also safe and acceptable development and prevalence of this and similar upcoming materials.

• Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. A. Takagi, A. Hirose, T. Nishimura, et al. 2008;33(1):105-16. PubMed · Publisher

  Abstract

  Nanomaterials of carbon origin tend to form various shapes of particles in micrometer dimensions. Among them, multi-wall carbon nanotubes (MWCNT) form fibrous or rod-shaped particles of length around 10 to 20 micrometers with an aspect ratio of more than three. Fibrous particles of this dimension including asbestos and some man-made fibers are reported to be carcinogenic, typically inducing mesothelioma. Here we report that MWCNT induces mesothelioma along with a positive control, crocidolite (blue asbestos), when administered intraperitoneally to p53 heterozygous mice that have been reported to be sensitive to asbestos. Our results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. To maintain sound activity of industrialization of nanomaterials, it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials both in the workplace and in the future market until the biological/ carcinogenic properties, especially of their long-term biodurability, are fully assessed.

• Re: Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. G. Ichihara, V. Castranova, A. Tanioka, et al. 2008;33(3):381-2; author reply 382-4. Comment · Letter PubMed · Publisher

• Risk of human health by particulate matter as a source of air pollution--comparison with tobacco smoking. M. Enomoto, W.J. Tierney, K. Nozaki. 2008;33(3):251-67. Review PubMed · Publisher

  Abstract

  Increased air pollution, containing carcinogenic particulate matter smaller than 2.5 microm (PM(2.5)), has gained particular attention in recent years as a causative factor in the increased incidence of respiratory diseases, including lung cancer. Extensive carcinogenicity studies conducted recently under Good Laboratory Practice conditions by National Toxicology Program in the USA, Ramazzini Foundation in Italy or Contract Research Organizations on numerous chemical compounds have demonstrated the importance of considering dose levels, times and duration of exposure in the safety evaluation of carcinogenic as well as classical toxic agents. Data on exposure levels to chemical carcinogens that produce tumor development have contributed to the evaluation of human carcinogens from extrapolation of animal data. A popular held misconception is that the risk from smoking is the result of inhaling assorted particulate matter and by products from burning tobacco rather than the very low ng levels of carcinogens present in smoke. Consider the fact that a piece of toasted bread contains ng levels of the carcinogen urethane (ethyl carbamate). Yet, no one has considered toast to be a human carcinogen. Future human carcinogenic risk assessment should emphasize consideration of inhalation exposure to higher levels of benzo (a) pyrene and other possible carcinogens and particulate matter present in polluted air derived from automobile exhaust, pitch and coal tar on paved roads and asbestos, in addition to other environmental contaminant exposure via the food and drinking water.

• Safety evaluation of titanium dioxide nanoparticles by their absorption and elimination profiles. K. Sugibayashi, H. Todo, E. Kimura. 2008;33(3):293-8. PubMed · Publisher

  Abstract

  If titanium dioxide nanoparticles are inert and non-biodegradable, they must be evaluated similarly to fullerenes, carbon nanotubes and asbestos. We surveyed the titanium level in typical raw food materials, and then intravenously injected titanium dioxide nanoparticles (primary particle diameter: 15 nm; secondary particle size: 220 nm) in mice and determined their tissue distribution and elimination. As a result, an unexpectedly high titanium concentration was observed in several foods. It was also detected in blood and tissues of healthy mice without administration of titanium dioxide nanoparticles. Then, forced i.v. injection of the nanoparticles was performed in mice. The titanim level was significantly increased in blood and tissues, but no increase was found in the brain after i.v. injection. Most titanium was concentrated in the liver after injection, but the liver level decreased over time (ca. 30% decrease in 1 month). These data show that titanium must be eliminated from the body, and suggest that we should reconsider an evaluation method for toxicity of titanium dioxide nanoparticles.

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