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Journal of Toxicological Sciences

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https://www.readbyqxmd.com/read/29142178/actual-consumption-amount-of-personal-care-products-reflecting-japanese-cosmetic-habits
#1
Masahiko Yamaguchi, Daisuke Araki, Takeshi Kanamori, Yasuko Okiyama, Hirokazu Seto, Masaki Uda, Masahito Usami, Yutaka Yamamoto, Takuji Masunaga, Hitoshi Sasa
Safety assessments of cosmetics are carried out by identifying possible harmful effects of substances in cosmetic products and assessing the exposure to products containing these substances. The present study provided data on the amounts of cosmetic products consumed in Japan to enhance and complement the existing data from Europe and the United States, i.e., the West. The outcomes of this study increase the accuracy of exposure assessments and enable more sophisticated risk assessment as a part of the safety assessment of cosmetic products...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142177/perinatal-exposure-to-tetrabromobisphenol-a-tbbpa-a-brominated-flame-retardant-exacerbated-the-pneumonia-in-respiratory-syncytial-virus-rsv-infected-offspring-mice
#2
Wataru Watanabe, Akihiko Hirose, Tomomi Takeshita, Seiko Hashiguchi, Kentaro Sakata, Katsuhiko Konno, Aki Miyauchi, Toshi Akashi, Hiroki Yoshida, Chihiro Sugita, Masahiko Kurokawa
To investigate the effects of perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, on the immune system, a respiratory syncytial virus (RSV) infection mouse model was utilized. Female mice were exposed to TBBPA mixed with the diet from 10 days after conception to weaning on postnatal day 21. Offspring mice were infected intranasally with A2 strain of RSV. Although no general toxicological sign was observed, the pulmonary viral titers of offspring mice exposed to 0.1% TBBPA were significantly increased compared with the control on day 5 post-infection...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142176/evaluation-of-the-human-relevance-of-the-constitutive-androstane-receptor-mediated-mode-of-action-for-rat-hepatocellular-tumor-formation-by-the-synthetic-pyrethroid-momfluorothrin
#3
Yu Okuda, Masahiko Kushida, Hiroko Kikumoto, Yoshimasa Nakamura, Hashihiro Higuchi, Satoshi Kawamura, Samuel M Cohen, Brian G Lake, Tomoya Yamada
High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142175/macrophage-differentiation-induced-by-pma-is-mediated-by-activation-of-rhoa-rock-signaling
#4
Lifeng Yang, Fan Dai, Lian Tang, Yulan Le, Wenjuan Yao
In order to investigate the effects of RhoA/ROCK signaling in macrophage differentiation, we used 100 ng/mL PMA to induce macrophage differentiation from U937 cells in vitro. The observation of cell morphology and the expression of CD68 and SR-A were performed to confirm the differentiation induced by PMA. Western blot analysis showed that the expression of ROCK1 and ROCK2 and the phosphorylation of MYPT1 were significantly increased after PMA treatment. Pulldown assay showed that the activation of RhoA was obviously enhanced when U937 cells were treated with PMA...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142174/evaluation-system-for-arrhythmogenic-potential-of-drugs-using-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-and-gene-expression-analysis
#5
Arisa Higa, Hirotaka Hoshi, Yuka Yanagisawa, Emi Ito, Gaku Morisawa, Jun-Ichi Imai, Shinya Watanabe, Motoki Takagi
In recent years, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been widely used to develop evaluation systems for drug cardiotoxicity, including the arrhythmia caused by QT prolongation. To accurately assess the arrhythmogenic potential of drugs, associated with QT prolongation, we developed an evaluation system using hiPS-CMs and gene expression analysis. hiPS-CMs were treated with 8 arrhythmogenic and 17 non-arrhythmogenic drugs at several concentrations for 24 hr to comprehensively analyze gene expression...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142173/effect-of-dibutyltin-on-placental-and-fetal-toxicity-in-rat
#6
Satoshi Furukawa, Naho Tsuji, Yoshiyuki Kobayashi, Yoshikazu Yamagishi, Seigo Hayashi, Masayoshi Abe, Yusuke Kuroda, Masayuki Kimura, Chisato Hayakawa, Akihiko Sugiyama
In order to elucidate the effect of chorioallantoic and yolk sac placenta on the embryonic/fetal toxicity in dibutyltin dichloride (DBTCl)-exposed rats, we examined the histopathological changes and the tissue distribution of dibutyltin in the placentas and embryos. DBTCl was orally administered to the groups at doses of 0 mg/kg during gestation days (GD)s 7-9 (control group) and 20 mg/kg during GDs 7-9 (GD7-9 treated group), and GDs 10-12 (GD10-12 treated group). The total fetal mortality was increased, and malformations characterized by craniofacial dysmorphism were detected in the GD7-9 treated group...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142172/change-in-redox-state-and-heat-shock-protein-expression-in-an-indian-major-carp-cirrhinus-cirrhosus-exposed-to-zinc-and-lead
#7
Mahammed Moniruzzaman, Puja Midday, Anindita Dhara, Debjit Das, Indranath Ghosal, Debosree Mukherjee, Suman Bhusan Chakraborty
Fish are exposed to different heavy metals that may induce numerous physiological changes. In the present study, we examined the redox state in response to a severe stress resulting from two heavy metals (Zinc and Lead) contamination in carp Cirrhinus cirrhosus. Fish were exposed to 1/10th of LC50 of the respective metals [zinc chloride (2.72 mg/L) and lead acetate (2.53 mg/L)] for 30 days and allowed to recover for another 30 days without any metal exposure. Concentration of metals, different enzymatic and non-enzymatic antioxidant agents and expression levels of heat shock protein (HSP) 70 and 90 were measured in the liver and the kidney of fish...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142171/sub-toxic-concentrations-of-nano-zno-and-nano-tio2-suppress-neurite-outgrowth-in-differentiated-pc12-cells
#8
Tomohiko Irie, Tsuyoshi Kawakami, Kaoru Sato, Makoto Usami
Nanomaterials have been extensively used in our daily life, and may also induce health effects and toxicity. Nanomaterials can translocate from the outside to internal organs, including the brain. For example, both nano-ZnO and nano-TiO2 translocate into the brain via the olfactory pathway in rodents, possibly leading to toxic effects on the brain. Although the effects of nano-ZnO and nano-TiO2 on neuronal viability or neuronal excitability have been studied, no work has focused on how these nanomaterials affect neuronal differentiation and development...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142170/characterization-of-a-rat-model-of-moderate-liver-dysfunction-based-on-alpha-naphthylisothiocyanate-induced-cholestasis
#9
Melanie K Bothe, Christoph Meyer, Udo Mueller, Jean-Christophe Queudot, Virginie Roger, Johannes Harleman, Martin Westphal
Plasma amino acid level changes occur in mild, moderate and severe stages of liver injury in human patients. In animal models, however, data are mainly restricted to severe liver injury models in rats. Here we present the characterization of a rat model of moderate liver dysfunction secondary to alpha-napthylisothiocyanate (ANIT)-induced cholestasis. Rats treated with 30 mg/kg/day ANIT for 3 weeks exhibited a time-dependent increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin levels and a decrease in albumin concentration...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142169/the-effects-of-ethylene-glycol-monomethyl-ether-on-female-reproductive-system-in-juvenile-rats
#10
Yoshikazu Taketa, Hiroshi Mineshima, Etsuko Ohta, Kyoko Nakano-Ito
Ethylene glycol monomethyl ether (EGME), which is widely used in various industrial products, is known for adverse effects on the reproductive system in adult rats. However, the effects of EGME on reproductive development in juvenile rats have not been demonstrated. In order to investigate the effects of EGME on the female reproductive system and pubertal development in juvenile rats, EGME was administered to female Sprague Dawley rats from postnatal day 21 to 41 at a dose level of 0, 50, 100, or 300 mg/kg...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142168/background-data-on-nod-shi-scid-il-2r%C3%AE-null-mice-nog-mice
#11
Kenichiro Kasahara, Yachiyo Fukunaga, Saori Igura, Rie Andoh, Tsubasa Saito, Isamu Suzuki, Hiroyuki Kanemitsu, Daisuke Suzuki, Ken Goto, Daichi Nakamura, Masahiro Mochizuki, Masahiko Yasuda, Ryo Inoue, Kazutoshi Tamura, Mariko Nagatani
To obtain background data of NOD/Shi-scid IL-2Rγ(null) (NOG) mice, severely immunedeficient mice, a total of 120 animals were examined at 7, 26 and 52 weeks-old (20 mice/sex/group). The survival rate at 52 weeks-old was 95% (19/20) in both sexes. Clinically, circling behavior in one direction along the cage wall was observed in males after 8 weeks and females after 47 weeks-old, and hunchback position was found in males after 32 weeks-old. Hematologically, lymphocyte count markedly decreased at all ages, while white blood cell count increased in several mice at 52 weeks-old...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142167/synergistic-cytotoxicity-caused-by-forming-a-complex-of-copper-and-2-9-dimethyl-1-10-phenanthroline-in-cultured-vascular-endothelial-cells
#12
Takehiro Nakamura, Eiko Yoshida, Tomoya Fujie, Fumihiko Ogata, Chika Yamamoto, Naohito Kawasaki, Toshiyuki Kaji
Organic-inorganic hybrid molecules, which are composed of organic-ligand(s) and metal(s), are indispensable as synthetic reagents in chemistry, but they have made very little in the way of contributions to biological research. Previously, we reported that the cytotoxicity of organic-inorganic hybrid molecules in vascular endothelial cells depends on interactions between the intramolecular metal and ligand, but remains independent of the hydrophobicity of the intramolecular metal(s). Herein, we show a synergistic cytotoxicity produced by forming a complex of copper and 2,9-dimethyl-1,10-phenanthroline in vascular endothelial cells that depends on the intracellular accumulation of copper...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142166/fish-oil-feeding-reverses-hepatomegaly-and-disrupted-hepatic-function-due-to-the-lack-of-fxr-signaling
#13
Masaaki Miyata, Kouhei Shinno, Tomoki Kinoshita, Yuichi Kinoshita, Yoshimasa Sugiura
Mice lacking farnesoid X receptor (FXR) are used as a model for nonalcoholic fatty liver disease because their livers exhibit hepatomegaly, hepatic steatosis, and hepatic inflammation. The influence of fish oil feeding on hepatomegaly and disrupted hepatic function was investigated using female Fxr-null mice and wild-type mice fed a fish oil diet (2% fish oil and 2% corn oil) or a control diet (4% corn oil) for 4 weeks. Hepatic n-3 polyunsaturated fatty acid (PUFA) levels, including 22:6 n-3 docosahexaenoic acid (DHA) and 20:5 n-3 eicosapentaenoic acid (EPA) were significantly higher in the fish oil group than those in the control group of Fxr-null mice and wild-type mice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142165/possible-mechanism-for-the-polychlorinated-bipheny-linduced-liver-selective-accumulation-of-thyroxine-in-rats
#14
Yoshihisa Kato, Aki Fujii, Koichi Haraguchi, Yukiko Fujii, Kazutaka Atobe, Tetsuya Endo, Osamu Kimura, Nobuyuki Koga, Chiho Ohta, Shizuo Yamada, Masakuni Degawa
We have previously reported that decrease in level of serum thyroxine T4 by Kanechor 500 (KC500) in rats would occur through the increase in hepatic T4 accumulation rather than the increase in hepatic T4-glucuronyl transferase activity. In the present study, to understand the mechanism underlying the KC500-mediated increase in hepatic T4 accumulation, we examined the relationship between the KC500-mediated changes in hepatic T4 accumulation and the expression levels of mRNAs of hepatic transporters including T4 transporters...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904300/hair-mercury-levels-in-relation-to-fish-consumption-among-vietnamese-in-hanoi
#15
Van Anh Thi Hoang, Hien Thu Thi Do, Tetsuro Agusa, Chihaya Koriyama, Suminori Akiba, Yasuhiro Ishibashi, Mineshi Sakamoto, Megumi Yamamoto
People are exposed to methylmercury (MeHg) mainly through fish consumption, which is increasing in Vietnam. However, little information is available on estimating the health risk of MeHg exposure through fish consumption in Vietnam. The present study examined the association between mercury (Hg) levels in hair and selenium (Se) levels in toenails of 196 Vietnamese people and their fish consumption, using a dietary questionnaire to obtain information pertinent for assessing health risk owing to MeHg exposure...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904299/a-cell-based-assay-using-heparg-cells-for-predicting-drug-induced-phospholipidosis
#16
Takafumi Tomida, Masakazu Ishimura, Masahiro Iwaki
The utility of HepaRG cells as an in vitro cell-based assay system for predicting drug-induced phospholipidosis (PLD) was investigated. In experiment 1, 10 PLD-positive compounds and 11 PLD-negative compounds were selected. HepaRG cells were treated with each compound for 48 hr. In experiment 2, loratadine and desloratadine, a major metabolite of loratadine, were used to assess metabolic activation for PLD. HepaRG cells were treated with loratadine and desloratadine in the presence or absence of 500 μM 1-aminobenzotriazole (ABT), a broad CYP inhibitor, for 48 hr...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904298/usefulness-of-urinary-biomarkers-for-nephrotoxicity-in-cynomolgus-monkeys-treated-with-gentamicin-cisplatin-and-puromycin-aminonucleoside
#17
Hiroshi Uchino, Junko Fujishima, Kaori Fukuoka, Teppei Iwakiri, Akira Kamikuri, Hidenori Maeda, Kazuhiro Nakama
The objective of this study was to investigate the availability of novel urinary biomarkers (BMs) such as total protein, albumin, β2-microglobulin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute nephrotoxicity in cynomolgus monkeys. Animals (total 9 males/3 groups) were administered gentamicin (GM) subcutaneously at 40 mg/kg for 7 days, cisplatin (CDDP) intravenously at 3 mg/kg once and puromycin aminonucleoside (PAN) intravenously at 20 mg/kg for 7 days...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904297/sex-differences-in-the-excretion-levels-of-traditional-and-novel-urinary-biomarkers-of-nephrotoxicity-in-rats
#18
Satoshi Tsuji, Masayuki Sugiura, Shunsuke Tsutsumi, Hisaharu Yamada
Urinary biomarkers have been used widely in preclinical toxicity studies to detect dysfunctions and injuries of the kidney caused by drugs under development. While they have been well studied for evaluating nephrotoxicity, knowledge of sex differences in excretion levels of urinary biomarkers remains inadequate. We conducted experiments focused on effects of endogenous sex hormones on urinary biomarkers using intact and castrated male and female rats. Comparisons of the urinary biomarker excretion levels between intact male and female rats at 5, 7, 9 and 12 weeks of age revealed higher excretion levels of leucine aminopeptidase (LAP), γ-glutamyl transpeptidase (γGTP), total protein, liver-type fatty acid-binding protein (L-FABP), cystatin C (Cys-C) and β2-microglobulin (β2-MG), and lower excretion level of kidney injury molecule 1 (Kim-1), in male rats as compared to female rats...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904296/developmental-changes-in-drug-metabolizing-enzyme-expression-during-metamorphosis-of-xenopus-tropicalis
#19
Junpei Mori, Seigo Sanoh, Keiko Kashiwagi, Hideki Hanada, Mitsuki Shigeta, Ken-Ichi T Suzuki, Takashi Yamamoto, Yaichiro Kotake, Kazumi Sugihara, Shigeyuki Kitamura, Akihiko Kashiwagi, Shigeru Ohta
A large number of chemicals are routinely detected in aquatic environments, and these chemicals may adversely affect aquatic organisms. Accurate risk assessment requires understanding drug-metabolizing systems in aquatic organisms because metabolism of these chemicals is a critical determinant of chemical bioaccumulation and related toxicity. In this study, we evaluated mRNA expression levels of nuclear receptors and drug-metabolizing enzymes as well as cytochrome P450 (CYP) activities in pro-metamorphic tadpoles, froglets, and adult frogs to determine how drug-metabolizing systems are altered at different life stages...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28904295/multidirectional-analyses-of-hepatic-chronotoxicity-induced-by-cadmium-in-mice
#20
Nobuhiko Miura, Hiroki Yoshioka, Atsushige Ashimori, Katsumi Ohtani, Tatsuya Hasegawa, Gi-Wook Hwang, Masayuki Ikeda, Tsunemasa Nonogaki
The expression levels or activities of biological defense factors can fluctuate daily following biological rhythms. We have focused on the relationship between injection timing and the degree of toxicity of cadmium (Cd) to promote the concept of "chronotoxicology," which introduces chronobiology to the field of toxicology. Our previous studies have clearly indicated that Cd may be subject to chronotoxicity. In this report, to confirm the character of the Cd-induced chronotoxicity, we performed multidirectional examinations...
2017: Journal of Toxicological Sciences
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