Chemicals Evaluation and Research Institute

Saitama, Japan

Chemicals Evaluation and Research Institute

Saitama, Japan
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Umano T.,Chemicals Evaluation and Research Institute | Tanaka R.,Biosafety Research Center Foods | Yamasaki K.,Chemicals Evaluation and Research Institute
Archives of Toxicology | Year: 2012

The purpose of this study was to investigate the endocrine-mediated effects of 4,4'-(hexafluoroisopropylidene)diphenol according to OECD test guideline no. 407. The estrogenic properties of this chemical have already been shown on uterotrophic assay, and this chemical is classified as a low-production volume chemical in REACH program. Rats were orally gavaged with 0, 10, 30, and 100 mg/kg/day of test chemical for at least 28 days, beginning at 8 weeks of age. In the 100 mg/kg group of male rats, endocrine-mediated effects, atrophic changes in the mammary glands and testicular Leydig cells, decreased accessory sex organ weights, and hypertrophy of the adrenal zona fasciculata with increased organ weights were seen; there was dysfunction of the estrous cycle in the 30 and 100 mg/kg groups, and increased serum T4 values were observed in the 100 mg/kg groups of both sexes. In addition, we also noted other findings, such as reduced body weight gains in the 30 and/or 100 mg/kg groups of both sexes, dilatation of the large intestinal lumen in the 100 mg/kg groups of both sexes, decreased hematopoiesis in the bone marrow and spleen, and decreased white blood cell counts in the 100 mg/kg group of male rats. Our results demonstrate that in a repeated-dose toxicity study, 4,4'-(hexafluoroisopropylidene)diphenol has various endocrine-mediated effects and its NOAEL (no observed adverse effect level) is 10 mg/kg/day. © 2011 Springer-Verlag.


Kayashima T.,Chemicals Evaluation and Research Institute | Kayashima T.,Kyushu Institute of Technology | Suzuki H.,Chemicals Evaluation and Research Institute | Maeda T.,Kyushu Institute of Technology | Ogawa H.I.,Kyushu Institute of Technology
Chemosphere | Year: 2013

We developed a detection method that uses quantitative real-time PCR (qPCR) and the TaqMan system to easily and rapidly assess the population of aniline-degrading bacteria in activated sludge prior to conducting a biodegradability test on a chemical compound. A primer and probe set for qPCR was designed by a multiple alignment of conserved amino acid sequences encoding the large (α) subunit of aniline dioxygenase. PCR amplification tests showed that the designed primer and probe set targeted aniline-degrading strains such as Acidovorax sp., Gordonia sp., Rhodococcus sp., and Pseudomonas putida, thereby suggesting that the developed method can detect a wide variety of aniline-degrading bacteria. There was a strong correlation between the relative copy number of the α-aniline dioxygenase gene in activated sludge obtained with the developed qPCR method and the number of aniline-degrading bacteria measured by the Most Probable Number method, which is the conventional method, and a good correlation with the lag time of the BOD curve for aniline degradation produced by the biodegradability test in activated sludge samples collected from eight different wastewater treatment plants in Japan. The developed method will be valuable for the rapid and accurate evaluation of the activity of inocula prior to conducting a ready biodegradability test. © 2013 Elsevier Ltd.


Sakamaki H.,Gifu University | Sakamaki H.,Chemicals Evaluation and Research Institute | Uchida T.,Chemicals Evaluation and Research Institute | Lim L.W.,Gifu University | Takeuchi T.,Gifu University
Journal of Chromatography A | Year: 2015

The influences of column hardware, such as chromatographic tubes and frits, on liquid chromatography-mass spectrometry (LC-MS) analysis of phosphorylated compounds were evaluated. The signal to noise ratio (S/N) and the intensity of flavin adenine dinucleotide (FAD) using a glass lined tube and polyethylene frit (GL-PE) column was approximately 170 and 90 times higher, respectively, than those using conventional stainless steel tube and stainless steel frit (S-S) column. In addition, the retention time of FAD using GL-PE column was the shortest compared to other columns. Interaction between phosphorylated compounds and metal ions in the flow path in the S-S column was stronger than that between them and the GL-PE column. Thus, the metal ions in the flow path in GL-PE column were low. Since the specific surface area of a pair of frits was 70 times larger than that of a chromatographic tube (150. mm × 2.1. mm), the frits were found to have more effective improvement of the S/N as well as the intensity than the chromatographic tubes, when phosphorylated compounds were analyzed by LC-MS. When the evaluated phosphorylated compounds were analyzed by LC-MS(/MS) using a GL-PE column, the intensity and S/N were increased. © 2015 Elsevier B.V.


Nassef M.,Kyushu University | Kim S.G.,Kyushu University | Seki M.,Chemicals Evaluation and Research Institute | Kang I.J.,Kyushu University | And 3 more authors.
Chemosphere | Year: 2010

We examined the toxicity of three pharmaceuticals and personal care products (PPCPs) - triclosan (TCS), diclofenac (DCF), and carbamazepine (CBMZ) - on embryonic development of Japanese medaka (Oryzias latipes) using in ovo nanoinjection. Medaka eggs (8 h post-fertilization; late blastula stage) were injected with 0.5 nL of triolein (vehicle control) or 0.5 nL of PPCPs, using different doses of TCS (1, 5, or 9 ng), DCF (1, 5, or 12 ng), or CBMZ (1, 5, or 12 ng) per egg in triolein, in addition to uninjected control. Following injection, we recorded survival, embryonic lesions, delay in embryonic development (eye, embryonic body and internal organs), heart beat rate, hatchability, and hatching time of embryos and upward swimming of larvae. As a result, injected PPCPs caused toxic responses to medaka embryos during embryonic development and around the day of hatching. Based on estimated EC50 values of PPCPs doses on survival of injected embryos at hatching, TCS (at a dose of 4.2 ng egg-1) was generally more toxic to medaka embryos, followed by DCF (6.0 ng egg-1), and CBMZ (13.1 ng egg-1). We conclude that the nanoinjection medaka embryos model is a valuable tool for analyzing the effects of chemicals on the development of fish embryos and feasibility of nanoinjecting PPCPs into small fish eggs perhaps mimicking early exposure resulting from oocyte uptake of contaminants from maternal extra gonadal tissues. © 2010 Elsevier Ltd. All rights reserved.


Makino Y.,University of Tokyo | Ichimura M.,University of Tokyo | Oshita S.,University of Tokyo | Kawagoe Y.,University of Tokyo | Yamanaka H.,Chemicals Evaluation and Research Institute
Food Chemistry | Year: 2010

The oxygen uptake rate of tomato fruits was estimated by an artificial neural network (ANN) model using near-infrared (NIR) spectral absorbance and fruit mass. The absorption peak apex from cytochrome c oxidase (COX) was confirmed at 841 nm for mitochondrial preparation and at 833 nm for intact fruits. The results of a proteome analysis that detected the putative COX subunit II PS17 from the mitochondrial preparation biochemically supported the presence of the absorption peak due to COX. An ANN model for estimating O2 uptake rate was developed from the absorbance data at 11 wavelengths from 645 to 979 nm including 833 nm and fruit mass as input variables. The O2 uptake rate was estimated by the proposed model with a correlation coefficient of 0.79 and a standard error of prediction of 0.091 mmol kg-1 h-1. This method may be effective for rapid estimation of shelf life and physiological activity of tomato fruits. © 2009 Elsevier Ltd. All rights reserved.


Takeshita J.-I.,Japan National Institute of Advanced Industrial Science and Technology | Seki M.,Chemicals Evaluation and Research Institute | Kamo M.,Japan National Institute of Advanced Industrial Science and Technology
Environmental Toxicology and Chemistry | Year: 2016

Loewe's additivity (concentration addition) is a well-known model for predicting the toxic effects of chemical mixtures under the additivity assumption of toxicity. However, from the perspective of chemical risk assessment and/or management, it is important to identify chemicals whose toxicities are additive when present concurrently, that is, it should be established whether there are chemical mixtures to which the concentration addition predictive model can be applied. The objective of the present study was to develop criteria for judging test results that deviated from the predictions by the concentration addition chemical mixture model. These criteria were based on the confidence interval of the concentration addition model's prediction and on estimation of errors of the predicted concentration–effect curves by toxicity tests after exposure to single chemicals. A log–logit model with 2 parameters was assumed for the concentration–effect curve of each individual chemical. These parameters were determined by the maximum-likelihood method, and the criteria were defined using the variances and the covariance of the parameters. In addition, the criteria were applied to a toxicity test of a binary mixture of p-n-nonylphenol and p-n-octylphenol using the Japanese killifish, medaka (Oryzias latipes). Consequently, the concentration addition model using confidence interval was capable of predicting the test results at any level, and no reason for rejecting the concentration addition was found. Environ Toxicol Chem 2016;35:1806–1814. © 2015 SETAC. © 2015 SETAC


Miwa S.,Chemicals Evaluation and Research Institute | Ohtake Y.,Chemicals Evaluation and Research Institute | Kawahara S.,Nagaoka University of Technology
Polymer Degradation and Stability | Year: 2016

Effect of ozone-charged water on degradation of silicone rubber, i.e., crosslinked polydimethylsiloxane/silica composite, was investigated by various analytical techniques, in which active species including active oxygen were generated by self-decomposition of ozone in water. The composite was less swollen with good solvent after degradation with ozone-charged water, whereas amount of extracted polydimethylsiloxane increased significantly, reflecting chain scission of the polymer. Hardness of the composite, measured with scanning probe microscope and hardness tester, was found to increase after degradation. The extracts were proved to be polydimethylsiloxane through FT-IR and GC-MS. The composite was characterized through DD/MAS and CP/MAS solid state NMR spectroscopies on 13C and 29Si nuclei. It was found that -O-Si(OH)(CH3) groups were made in polydimethylsiloxane due to oxidative reaction with hydroxyl radical and they were attracted to silica in the composite to result in the decrease in the swelling ratio and the increase in the hardness. © 2016 Elsevier Ltd. All rights reserved.


Yamasaki K.,Chemicals Evaluation and Research Institute | Okuda H.,Japan Bioassay Research Center
Toxicology Letters | Year: 2012

The purpose of this study was to compare endocrine-mediated effects of bisphenol A related compounds, 2,2-bis(4-cyanatophyenyl)propane and 4,4'-cyclohexylidenebisphenol with reference to OECD Test Guideline No. 407. Rats were orally gavaged with 0, 4, 20, and 100. mg/kg/day of 2,2-bis(4-cyanatophyenyl)propane, and 0, 30, 100, and 300. mg/kg/day of 4,4'-cyclohexylidenebisphenol for at least 28 days beginning at 8 weeks of age. Endocrine-mediated effects were not observed in rats given 2,2-bis(4-cyanatophyenyl)propane. Male accessory sex organ weights decreased in the 4,4'-cyclohexylidenebisphenol 300. mg/kg group and serum T4 values increased in all male groups treated with this compound. Our results suggest that endocrine-mediated changes caused by the present bisphenol related compound can be divided into estrogenic or thyroid hormonal effects, and estrogenic effects observed in the repeated-dose study were related to their estrogenic potency confirmed by uterotrophic assay. © 2011 Elsevier Ireland Ltd.


Kondo H.,Chemicals Evaluation and Research Institute | Ohtake Y.,Chemicals Evaluation and Research Institute
Journal of Applied Polymer Science | Year: 2010

Natural rubber (NR) containing fullerenol, C60-OH, was prepared by two methods; one by mixing C60-OH aqueous solution to NR latex followed by coagulation (wet method) and the other by mixing C60-OH powder with solid rubber by an open roll mixer (dry method). C60-OH mixed by wet method was homogeneously dispersed in the rubber, while one mixed by dry method was particles in the size up to 70 μm. The former exhibited large reinforcing and antiaging effect than the latter. The large antiaging effect was explained by the finding that C60-OH had large radical scavenging ability and gel forming ability during heat treatment. © 2010 Wiley Periodicals, Inc.


Matsumoto H.,Chemicals Evaluation and Research Institute | Saito F.,Chemicals Evaluation and Research Institute | Takeyoshi M.,Chemicals Evaluation and Research Institute
Journal of Toxicological Sciences | Year: 2014

Carcinogenicity is one of the most serious toxic effects of chemicals, and highly accurate methods for predicting carcinogens are strongly desired for human health. Here, we developed a new prediction system named “CARCINOscreen®” for evaluating the carcinogenic potentials of chemicals using the gene expression profiles of liver tissues from rats after a 28-day repeated dose toxicity study. The prediction formula was generated using a support vector machine with predictive genes selected from 68 training chemical datasets; a predictive score was then calculated to predict the carcinogenic potentials of the tested chemicals. To ensure the accuracy of the prediction system, the chemicals were divided into three groups (Groups 1 to 3) according to the resulting hepatic gene expression profiles, and a prediction formula was generated for each group. The prediction system was capable of predicting the carcinogenic-ity of training carcinogens and non-carcinogens with an accuracy of 92.9% to 100%. The final prediction result was determined based on the maximum prediction value obtained with three independent prediction formulas to build up the CARCINOscreen®. The system was able to predict carcinogenicity accurately in 94.1% of the 68 training chemicals. An external validation trial was performed with 16 chemicals, consisting of various carcinogens targeting rat liver or other organs and non-carcinogens. The system identified 68.8% of all the chemicals and 100% of the rat liver carcinogens as carcinogens. Thus, the CARCI-NOscreen®, a novel system for predicting hepatocarcinogenicity, is a promising tool for the prediction of rat liver carcinogens. © 2014, Japanese Society of Toxicology. All rights reserved.

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