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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 Source

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. Source

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. Source

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. Source

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. Source

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