研究業績

研究業績
論文等

免疫毒性学
Effective induction of oral anaphylaxis to ovalbumin in mice sensitized by feeding of theantigen with aid of oil emulsion and salicylate
Tomoko SHINDO, Yukiko KANAZAWA1, Yoshiaki SAITO, Kohichi KOJIMA, Motoyasu OHSAWA, Reiko TESHIMA2
Journal of Toxicological Sciences, 2012; 37 ( 2 ): 307- 315
It is important to evaluate the ability of novel proteins in food crops and products to elicit
potentially harmful immunologic responses, including allergic hypersensitivity. We developed anovel mouse model of food allergy involving an oral challenge of a protein antigen after feeding of
the antigen in combination with modulating factors often ingested in daily life, namely, dietary
oil emulsion and salicylate. In the model, BALB/c mice were sensitized orally for three weeks with
ovalbumin (OVA) in linoleic acid/lecithin emulsion, followed immediately by intraperitoneal injectionof sodium salicylate. At the end of the sensitization, the incidence of mice positive for serum OVAspecific IgG 1 but not IgE had significantly increased in the combined-sensitization group. Afterthe 3 -week sensitization, a single or double oral challenge with OVA effectively and significantly
caused severe anaphylaxis, as compared with the groups sensitized with OVA in the emulsion or
the vehicle alone. Moderate increase of plasma histamine and intestinal abnormality in histology
was found only in the combined-sensitization group. Anaphylaxis symptoms in the sensitized mice
were induced more by oral challenge than by intravenous challenge, suggesting a critical role forthe mucosal system. This is the first model for successful induction of oral anaphylaxis in mice
sensitized by feeding of food protein without adjuvant. It will be useful to elucidate the mechanismof food allergy and to detect modulating factors of oral allergy at sensitization using this model,
which simulates real life conditions.
1

Pharmaceuticals and Medical Devices Agency; 2 Division of Biochemistry and

Immunochemistry, National Institute of Health Sciences

実験動物学
Male Hatano high-avoidance rats show high avoidance and high anxiety-like behaviors
as compared with male low-avoidance rats
Yasuyuki HORII1,2, Maiko KAWAGUCHI3,4, Ryo OHTA, Akihiro HIRANO3,4, Gen WATANABE1,2,
Nobumasa KATO5,6, Toshiyuki HIMI4, Kazuyoshi TAYA1,2
Experimental Animals, 2012; 61 ( 5 ): 517 - 524
Our prime objective was to establish an optimal model animal for studying avoidance learningand memory in rodents. The two-way rat inbred strains of Hatano high- (HAA) and low-avoidance(LAA) animals were originally selected and bred in accordance with their high or low performance
respectively in the shuttle-box active avoidance task. Previous studies demonstrated that they have14

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clear strain differences in endocrine stress response, which is related to acquisition of aversive
learning and emotional reactivity. To evaluate the effect of selection by the shuttle-box task on
avoidance performance and emotional reactivity, male Hatano rats underwent passive avoidance,
open field and elevated plus maze tests. The present results show that the avoidance performancein the passive task was significantly greater in HAA rats than in LAA rats. Furthermore, HAA rats
showed high anxiety-like behaviors compared with LAA rats in open field and elevated plus maze
tests. Taken together, this study demonstrated that 1) selection and breeding of Hatano HAA and
LAA strain rats by shuttle-box task had been properly carried out with the criterion of high andlow avoidance performance respectively and that 2 ) HAA rats were predisposed to high anxiety
compared with LAA rats. These results indicated that Hatano HAA and LAA rats can be usefulmodels for studying avoidance learning and memory.
1

Department of Basic Veterinary Science, United Graduate School of Veterinary Sciences,

Gifu University; 2 Laboratory of Vererinary Physiology, Tokyo University of Agriculture andTechnology; 3 School of Agriculture, Meiji University; 4 Faculty of Pharmacy and ResearchInstitute of Pharmaceutical Science, Musashino University; 5 Department of Psychiatry, Showa
University School of Medicine; 6 JST, CREST

毒性病理学
PAM 染色におけるコントロールサーベイ報告
木村正美 1 , 中野健二 2 , 国遠かおり 3 , 山口

肇 , 今田輝義 4 , 古川文夫 5 , 阿倍

寛 6 , 打屋尚章 7

実験病理組織技術研究会誌 , 2012 ; 21 ( 1 ): 1-33
1

株式会社サンプラネット安全性研究ユニット ; 2 アステラスリサーチテクノロジー株式会社 ;3

大日本住友製薬株式会社 ; 4 協和発酵キリン株式会社 , 5 株式会社 DIMS 医科学研究所 ;6

順天堂大学医学部病理学第一講座 ; 7 国立がんセンター研究所

第 19 回技術研修会グループミーティングのまとめ

実験病理技術全般について

島田美千代 , 萩原 孝 , 位坂清継 , 五十嵐功 , 国遠かおり 5 , 前田圭子 6 , 三好貴子 7 , 山口 肇 , 中野健二 8
1

2

3

4

実験病理組織技術研究会誌 , 2012 ; 21 ( 1 ): 35 -43
1

株式会社サンプラネット安全性研究ユニット ; 2 公益財団法人食品農医薬品安全性評価センター;

3

扶桑薬品工業株式会社研究開発センター; 4 第一三共株式会社安全性研究所 ;5

大日本住友製薬株式会社 ; 6 住友化学株式会社生物環境科学研究所 ;7

塩野義製薬株式会社新薬研究所 ; 8 アステラスリサーチテクノロジー株式会社

第 19 回技術研修会アンケート集計結果報告

実験病理技術全般について

前田圭子 , 五十嵐功 , 位坂清継 , 国遠かおり , 島田美千代 5 , 萩原 孝 6 , 三好貴子 7 , 山口 肇 , 中野健二 8
1

2

3

4

実験病理組織技術研究会誌 , 2012 ; 21 ( 1 ): 45- 52
1住友化学株式会社生物環境科学研究所 ; 2 第一三共株式会社安全性研究所 ; 3 扶桑薬品工業株式会社

研究開発センター; 4 大日本住友製薬株式会社 ; 5 株式会社サンプラネット安全性研究ユニット ; 6 公益財団法人食品農医薬品安全性評価センター; 7 塩野義製薬株式会社新薬研究所 ; 8 アステラスリサーチ
テクノロジー株式会社

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生殖・発生毒性学
Assessment of technical protocols for novel embryonic stem cell tests with molecularmarkers (Hand1- and Cmya1-ESTs): a preliminary cross-laboratory performance analysis
Noriyuki SUZUKI1, Norihisa YAMASHITA1, Naoteru KOSEKI2, Toru YAMADA2, Yutaka KIMURA3,
Setsuya AIBA3, Tomoyasu TOYOIZUMI, Mika WATANABE, Ryo OHTA, Noriho TANAKA, Koichi SAITO1
Journal of Toxicological Sciences, 2012; 37 ( 4 ): 845- 851
The Hand 1 - and Cmya 1 -ESTs are novel short-term tests for embryotoxic chemicals using
genetically engineering mouse ES cells for luciferase reporter gene assays. These ESTs allow
convenient determination of differentiation toxicity and cell viability in a short duration with highthroughput 96-well microplates for prediction of embryotoxicity of chemicals. To assess the Hand 1 EST technical protocol, we firstly compared reporter gene assay and cytotoxicity test data for arepresentative compound (hydroxyurea) from four different laboratories with tests carried out
under the same experimental conditions. Extensive investigations of the Hand 1- and Cmya 1 -ESTs
were then performed to explore reproducibility by comparing a set of 6 well-known test chemicals,
including hydroxyurea, across the laboratories. The results gave good correspondence in all four
laboratories, indicating that transferability, intra-laboratory variability and inter-laboratory
variability of the present technical protocols of the ESTs were sufficient to conduct further
validation studies.
1

Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.; 2 Safety ResearchLaboratories, Dainippon Sumitomo Pharma Co., Ltd.; 3 Department of Dermatology, Tohoku
University Graduate School of Medicine
Ovariectomized mouse uterotrophic assay of 36 chemicals
Ryo OHTA, Atsuya TAKAGI1, Hideo OHMUKAI, Hideki MARUMO, Atsushi ONO1, Yuko MATSUSHIMA1,
Tohru INOUE1, Hiroshi ONO, Jun KANNO1
Journal of Toxicological Sciences, 2012; 37 ( 5 ): 879- 889
The concern over endocrine disruptors prompted international establishment of a strategic
framework for the identification of the estrogenic compounds. OECD has launched the Conceptual
Framework tool box containing various screening and testing methods including the uterotrophic
assay. The (anti)estrogenicity of 36 chemicals suspected to be estrogen-receptor interactive by insilico and/or in vitro screening in the Extended Scheme for Endocrine Disruptor Screening andTesting of the Ministry of Health, Labour and Welfare, Japan, were monitored by the uterotrophic
assay using C57BL/6J ovariectomized adult female mice after a 7-day exposure by oral gavage (po)and subcutaneous injection (sc). Ethynyl estradiol was used as reference for agonist and antagonist
detection. In addition, Bisphenol A (sc) and Genistein (po) were tested for the comparison to rat assays.
Among the 36, 2-[Bis(4-hydroxyphenyl)methyl]benzylalcohol, 2,2’
,4,4’
-Tetrahydroxybenzophenone,
2 , 4 -Dihydroxybenzophenone, 3 , 3’
, 5 -Triiodothyroacetic acid, New fuchsin and alphaNaphtholbenzein, showed both estrogenic agonistic and antagonistic activities; first two showed
U-shaped dose-response in antagonistic studies. N,N-Diphenyl-p-phenylenediamine, 2 , 2’
-Dihydroxy-4,4’-dimethoxybenzophenone, n-Butyl 4-hydroxybenzoate, and Reserpine were agonistic
by sc. Benzo [a] pyrene, Benz [a] anthracene, Dibenz [a,h] anthracene, 2-(2H-Benzotriazol-2-yl)-4,6di(t-pentyl)phenol, Rosemarinic acid, meta-Thymol, 6 -Gingerol, Colchicine, Malachite green base,16

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Fenbuconazole, and Lead acetate were antagonistic. The rest, i.e. n-Heptyl 4 -hydroxybenzoate,
Tetrazolium violet, Pravastatin sodium salt, Physostigmine, salicylate ( 1: 1 ), Nordihydroguaiaretic
acid, o-Cresolphthalein, 1 , 3 -Dinitrobenzene, C.I. Pigment orange, Tetrabromobisphenol-A,
2 -Hydroxy- 4 -methoxybenzophenone, Ethylparaben, Propyl p-hydroxybenzoate, Kaempferol,2 -( 2 -Benzotriazolyl)-p-cresol and Phenolphthalein were negative for both effects. Taking together
with in silico/ in vitro screening, the result suggested that the ovariectomized mouse uterotrophic
bioassay has sufficient performance comparable to rat for the screening of (anti)estrogenicity ofvarious chemicals.
1

Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National

Institute of Health Sciences
Delayed reproductive dysfunction in female rats induced by early life exposure to lowdose diethylstilbestrol
Ryo OHTA, Hideo OHMUKAI, Hideki MARUMO, Tomoko SHINDO, Tomoko NAGATA, Hiroshi ONO
Reproductive Toxicology, 2012 ; 34 ( 3 ): 323- 330
A one-lifespan test was carried out to establish a test protocol for endocrine-disrupting chemicals(EDCs). Diethylstilbestrol (DES) was administered by oral gavage to neonatal rats at doses of 0 . 05 ,0 .5 and 5 µg/kg/day for 5 days after birth. Abnormal estrous cycles were observed throughout the
study in all females from the 5 µg/kg group, and in 40 % from the 0 . 5 µg/kg group from 24 weeks
of age. The conception rate of 12 -week-old females in the 5 µg/kg group was 0 %, and that of the
23-week-old females in the 0. 5 µg/kg group was 33 . 3 %. No effect of DES was observed at the first
parturition in any group, except for the 5 µg/kg group. However, litter size was significantly reducedin the 0.5 µg/kg group at the second parturition. These results indicated that a prolonged period of
observation of reproductive function is necessary to determine EDCs reliably.

細胞毒性学
Prevalidation study of the BALB/c 3T3 cell transformation assay for assessment ofcarcinogenic potential of chemicals
Noriho TANAKA, Susanne BOHNENBERGER1, Thorsten KUNKELMANN1, Barbara MUNARO2,
Jessica PONTI2, Albrecht POTH1, Enrico SABBIONI2, Ayako SAKAI, Susan SALOVAARA2,
Kiyoshi SASAKI, B. Claire THOMAS2, Makoto UMEDA
Mutation Research, 2012; 744 ( 1 ): 20 -29
The cell transformation assays (CTAs) have attracted attention within the field of alternative
methods due to their potential to reduce the number of animal experiments in the field ofcarcinogenicity. The CTA using BALB/c 3 T 3 cells has proved to be able to respond to chemical
carcinogens by inducing morphologically transformed foci. Although a considerable amount of dataon the performance of the assay has been collected, a formal evaluation focusing particularly on
reproducibility, and a standardised protocol were considered important. Therefore the European
Centre for the Validation of Alternative Methods (ECVAM) decided to coordinate a prevalidation
study of the BALB/c 3 T 3 CTA. Three different laboratories from Japan and Europe participated.
In the study the following modules were assessed stepwise: test definition (Module 1 ) consistedof the standardisation of the protocol, the selection of the cell lineage, and the preparation of a17

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photo catalogue on the transformed foci. The within-laboratory reproducibility (Module 2 ) and thetransferability (Module 3 ) were assessed using non-coded and coded 3 -methylcholanthrene. Then,
five coded chemicals were tested for the assessment of between-laboratory reproducibility (Module 4).
All three laboratories obtained positive results with benzo[a]pyrene, phenanthrene and o-toluidine
HCl. 2 -Acetylaminofluorene was positive in two laboratories and equivocal in one laboratory.
Anthracene was negative in all three laboratories. The chemicals except phenanthrene, which isclassified by IARC (http://monographs.iarc.fr) as group 3“not classifiable as to its carcinogenicity
to human”, were correctly predicted as carcinogens. Further studies on phenanthrene will clarify
this discrepancy. Thus, although only a few chemicals were tested, it can be seen that the predictive
capacity of the BALB/c 3 T3 CTA is satisfactory.
On the basis of the outcome of this study, an improved protocol, incorporating some changes
related to data interpretation, has been developed. It is recommended that this protocol be usedin the future to provide more data that may confirm the robustness of this protocol and theperformance of the assay itself. During the study it became clear that selecting the most appropriate
concentrations for the transformation assay is crucial.
1

Harlan Cytotest Cell Research GmbH; 2 European Centre for the Validation of Alternative

Methods, Institute for Health and Consumer Protection, Joint Research Centre of the European
Commission
Recommended protocol for the BALB/c 3T3 cell transformation assay
Kiyoshi SASAKI, Susanne BOHNENBERGER1, Kumiko HAYASHI, Thorsten KUNKELMANN1,
Dai MURAMATSU, Pascal PHRAKONKHAM2, Albrecht POTH1, Ayako SAKAI, Susan SALOVAARA2,
Noriho TANAKA, B. Claire THOMAS2, Makoto UMEDA
Mutation Research, 2012; 744 ( 1 ): 30 - 35
The present protocol has been developed for the BALB/c 3 T 3 cell transformation assay (CTA),
following the prevalidation study coordinated by the European Centre for the Validation of
Alternative Methods (ECVAM) and reported in this issue. Based upon the experience gained fromthis effort and as suggested by the Validation Management Team (VMT), some acceptance andassessment criteria have been refined compared to those used during the prevalidation study. The
present protocol thus describes cell culture maintenance, the dose-range finding (DRF) experimentand the transformation assay, including cytotoxicity and morphological transformation evaluation.
Use of this protocol and of the associated photo catalogue included in this issue is recommended forthe future conduct of the BALB/c 3 T3 CTA.
1Harlan Cytotest Cell Research GmbH; 2 European Centre for the Validation of Alternative Methods,

Institute for Health and Consumer Protection, European Commission Joint Research Centre
Photo catalogue for the classification of foci in the BALB/c 3T3 cell transformation assay
Kiyoshi SASAKI, Susanne BOHNENBERGER1, Kumiko HAYASHI, Thorsten KUNKELMANN1,
Dai MURAMATSU, Albrecht POTH1, Ayako SAKAI, Susan SALOVAARA2, Noriho TANAKA,
B. Claire THOMAS2, Makoto UMEDA
Mutation Research, 2012; 744 ( 1 ): 42- 53
This catalogue is a display of focus photos representative of the BALB/c 3T 3 cell transformation
assay (CTA). It is intended as a visual aid for the identification and the scoring of foci in the conduct18

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of the assay.
A proper training from experienced personnel together with the protocol reported in this issue andthe present photo catalogue will support method transfer and consistency in the assay results.
1

Harlan Cytotest Cell Research GmbH; 2 European Centre for the Validation of Alternative

Methods, Institute for Health and Consumer Protection, European Commission Joint ResearchCentre平成 22 年度
「日本薬局方の試験法に関する研究」研究報告

輸液用ゴム栓試験法の見直し研究（第 4 報）

―ゴム栓試験法：細胞毒性試験における試料溶液の調製方法に関する検討―柘植英哉 1 , 大内正1, 森充生 1 , 下田耕三 1 , 大庭澄明 1 , 青木光夫 2 , 林

山影康次 , 渡辺美香 , 田中憲穂 , 小島美則 2 , 五島隆志 2 ,

肇 3 , 四方田千佳子 3

医薬品医療機器レギュラトリーサイエンス , 2012 ; 43 ( 5 ): 473- 482
1

公益社団法人東京医薬品工業協会局方委員会 ; 2 大阪医薬品協会技術研究委員会 ;3

国立医薬品食品衛生研究所

遺伝毒性学
Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutanone, a radiolytic
product of palmitic acid, in human lymphoma U937 cells
Da-Yong YU1, Quing-Li ZHAO1, Masakazu FURUTA2, Setsuko TODORIKI3, Keisuke IZUMI4,
Kohji YAMAKAGE, Kozo MATSUMOTO5, Takaharu NOMURA6, Takashi KONDO1
Apoptosis, 2012 ; 17 ( 6 ): 636 - 645
The irradiation of fat-containing food forms 2-dodecylcyclobutanone (2-DCB) from palmitic acid (PA).
In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells.
We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB
and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis
induced by 2-DCB and PA was strongly prevented by an antioxidant, N-acetyl-L-cysteine. The treatment
with 2-DCB and PA resulted in the loss of mitochondrial membrane potential, and Fas, caspase-8
and caspase-3 activation. Pretreatment with a pan-caspase inhibitor (z-VAD) significantly inhibited
apoptosis induced by 2-DCB and PA. Moreover, 2-DCB and PA also induced Bax up-regulation, thereduction in Bcl-2 expression level, Bid cleavage and the release of cytochrome c from the mitochondria
to the cytosol. In addition, an increase in intracellular Ca2+ concentration ([Ca 2+]i) was observed after thetreatment with 2-DCB and PA. Our results indicated that intracellular ROS generation, the modulationof the Fas-mitochondrion-caspase-dependent pathway and the increase in [Ca 2+]i involved in apoptosis
are induced by 2-DCB and PA in U937 cells.
1

Department of Radiological Sciences, Graduate School of Medeicine and Pharmaceutical

Sciences, University of Toyama; 2 Laboratory of Quantum-Beam Chemistry and Biology,
Radiation Research Center, Osaka Prefecture University; 3 Food Safety Division, National Food
Research Institute; 4 Department of Molecular and Environmental Pathology, Institute of Health
Biosciences, The University of Tokushima Graduate School; 5 Department of Animal Medical
Sciences, Faculty of Life Sciences, Kyoto Sangyo University; 6 Radiation Safety Research Center,
Central Research Institute of Electric Power Industry

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Tissue sample preparation for in vivo rodent alkaline comet assay
Madoka NAKAJIMA1, Maya UEDA1, Kohji YAMAKAGE, Yuzuki NAKAGAWA, Munehiro NAKAGAWA2,
Wakako OHYAMA3, Takashi OMORI4, Norihide ASANO5, Makoto HAYASHI1, Yoshifumi UNO6
Genes and Environment, 2012 ; 34 ( 1 ): 50- 54
The Japanese Environmental Mutagen Society/the Mammalian Mutagenicity Study groupconducted a collaborative study to investigate whether cell nuclei or whole cells might be moresuitably used to correctly detect genotoxic chemicals in the in vivo rodent alkaline Comet assay.
Four participating laboratories applied four sample processing methods, i.e., three homogenization
methods using the usual Potter-type shaft, a customized (loose) Potter-type shaft, or a Downs-loosetype shaft, for preparing cell nuclei, and the mesh membrane method for preparing whole cells, tothe male rat liver. Homogenization with the usual Potter-type shaft clearly produced damage ofthe cell nuclei and DNA, while the other three methods seemed to provide similar conditions of thetissue samples. The proportion of cell nuclei: whole cells was 80 - 90 %: 10 - 20 % in all laboratories
when the samples were prepared by homogenization using a Downs-loose-type shaft or by the meshmembrane method. The %DNA in tail were comparable in both samples among the negative control
groups (single oral administration with physiological saline) of all laboratories, and showed an equal
degree of increase in both samples of the ethyl methanesulfonate groups (single oral administration
at 250 mg/kg) in all laboratories. In conclusion, the homogenization method using a loosely
customized Potter-type shaft or a Downs-loose-type shaft, and the mesh membrane method would
be equally acceptable for the in vivo rodent alkaline Comet assay.
1

Bioassay Research Center, Foods, Drugs and Pesticides; 2 Drug Development Service Segment,

Mitsubishi Chemical Medience Co.; 3 Yakult Central Institute for Microbiological Research;
4

Doshisha University; 5 Kinki University; 6 Safety Research Laboratories, Mitsubishi Tanabe

Pharma Co.
In vitro clastogenicity and phototoxicity of fullerene (C60) nanomaterials in mammalian cells
Masamitsu HONMA1, Toshitaka TAKAHASHI, Shin ASADA, Yuzuki NAKAGAWA, Atsuko IKEDA, Kohji YAMAKAGE
Mutation Research, 2012 ; 749 ( 1 - 2 ): 97- 100
Carbon nanomaterials such as carbon nanotubes, graphene, and fullerenes (C 60 ) are widelyused in industry. Because of human health concerns, their toxic potential has been examined invivo and in vitro. Here we used mammalian cells to examine the in vitro clastogenicity as well as
the phototoxicity of C 60 . While C 60 induced no structural chromosome aberrations in CHL/IU cells
at up to 5 mg/mL (the maximum concentration tested), it significantly induced polyploidy at 2 . 5
and 5 mg/mL with and without metabolic activation. In BALB 3 T3 cells, C 60 showed no phototoxic
potential but the anatase form of titanium oxide did. Since insoluble nanomaterials cause polyploidyby blocking cytokinesis rather than by damaging DNA, we concluded that the polyploidy induced by
C 60 in CHL/IU cells was probably due to non-DNA interacting mechanisms.
1

Division of Genetics and Mutagenesis, National Institute of Health Sciences20

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食品衛生学
特集「塩及び海水の分析法及び信頼性向上の最近の展開」（解説）
食の安全を確保するための外部精度管理渡辺卓穂
Bulletin of the Society of Sea Water Science, Japan, 2013; 67 ( 1 ): 12 - 18

動物実験代替法第 16 章コロニー形成法による細胞毒性試験（第十六改正日本薬局方；一般試験法「7.02 医薬品容器試験法」）(ISO10993-5 : Biological Evaluation of Medical Device – Part 5 : Tests for In Vitro Cytotoxicity)
渡辺美香
動物実験代替安全性試験プロトコル集

シーエムシー出版 , 東京 ( 2012 ) pp. 198- 210

医療機器
Biological evaluation and regulation of medical devices in Japan
Kohichi KOJIMA
Biocompatibility and Performance of Medical Devices, Woodhead Publishing Ltd., Cambridge, UK( 2012), pp. 404- 448
In Japan, unified guidelines for biological safety tests of medical devices have been implemented
since 1995. Since then, there have been no marked changes in the basic way of thinking. In recent
years, Japan’s way of thinking has been introduced into various parts of the ISO 10993 series,
and international understanding has also been promoted. The basic test methods used in Japando not differ from those used outside Japan for most test items. However, there is a perception gap
in sample preparation applied to these tests. In Japan, the basic stance is to eliminate all riskssystematically. This stance is especially prominent in cytotoxicity tests, sensitization tests andgenotoxicity tests. In addition, there is a perception gap also in classification. Focusing on thesepoints, this chapter outlines the Japanese guidance for biological safety tests of medical devices.
第2節

医療機器 GLP への対応

小島幸一
世界への薬事申請書の書き方
せるポイント

第2章

成功へのバイブル

第9部

医療機器の国内申請・薬事対応を成功さ

日本国内申請時における GXP 適合性調査への対応

技術情報協会 , 東京 (2012 )pp. 1019-1029

発達神経毒性学
Abnormal brain function of the rat neonate in a prenatal 5-bromo-2'-deoxyuridine(BrdU)-induced developmental disorder model
Tetsuo OGAWA1, Makiko KUWAGATA, Katsumasa MUNEOKA1, Chizu WAKAI1,
Mika SENUMA, Hiroko KUBO1, Seiji SHIODA1
International Journal of Developmental Neuroscience, 2012 ; 30 ( 6 ): 507 - 515
Neonatal brain function was investigated in a prenatal BrdU-induced developmental disorder21

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model, which has been reported to exhibit behavioral abnormalities such as locomotor hyperactivity,
impaired learning and memory, and lower anxiety in offspring. After 1 h home cage deprivation
we observed an increase in the number of c-Fos (neuronal activity marker) immunoreactive cells inseveral brain regions of the olfactory and stress-related areas in normal neonates at 11 days. Next,
pregnant rats were exposed to 50 mg/kg of BrdU from gestation days 9- 15, and their offspring at 11days were home-cage deprived. Compared to vehicle control, the number of c-Fos immunoreactive
cells in BrdU group was found to be decreased in the piriform cortex and locus coeruleus, which
are known to play an important role in neonatal learning and memory. We also analyzed Pearson
product-moment correlation coefficient of the number of c-Fos immunoreactive cells, focusing on
the piriform cortex and locus coeruleus versus numerous other brain areas ( 11 areas including
amygdala). Numerous significant correlations were observed in the vehicle control group,
however, correlations of the locus coeruleus disappeared in the BrdU group. By observing c-Fos
immunoreactivity after home cage deprivation our study uncovers abnormal brain functions as earlyas postnatal day 11 in this disorder model. Based on these results, we propose a new histologicalapproach for functional characterization of developmental disorder models.
1

Department of Anatomy, Showa University, School of Medicine

Current problems of in vivo developmental neurotoxicity tests and a new in vivo
approach focusing on each step of the developing central nervous system
Makiko KUWAGATA
Congenital Anomalies, 2012 ; 52 ( 3 ): 129- 139
Developmental neurotoxicity (DNT) tests usually focus on postnatal indicators, such as behavior
and neuropathology, for the detection of chemically induced neurodevelopmental defects in thecentral nervous system (CNS). However, low reliability, especially low reproducibility, of behavioral
results often causes concern among scientists and the scientific community in general. Guidance ofneurohistopathological examination in the DNT guideline also has some shortcomings, especiallyrelating to the methodological aspects. Ongoing international trends in DNT tests have shiftedfrom the use of original in vivo animal (mammalian) studies to in vitro experiments using cell
cultures and/or non-mammalian species, such as fish. In vitro systems might initially be usefulto screen test chemicals for their DNT potential. Although in vitro systems are employed asalternative approaches for DNT studies, the use of in vivo studies based on animal models remains
an important factor when data are to be extrapolated to the human case. In this review, a new invivo approach that focuses on histopathological observation of each developmental step of the CNS,
such as proliferation of neural stem cells, migration of immature neurons, and formation of neuralnetworks, using fetal and neonatal brains after chemical exposure is introduced, and some queries
and arguments for current DNT experimental guidelines are discussed.
Chapter 5 Sexual dimorphism in monoamine metabolism in BrdU-treated rats showing
behavioral dopamine hypersensitivity: An animal model of schizophrenia
Katsumasa MUNEOKA1, Makiko KUWAGATA
Sexual Dimorphism, InTech, Rijeka, Croatia (2013) pp. 81- 96
1Department of Anatomy, Showa University, School of Medicine

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研究業績

内分泌学
Estrogenic regulation of Kiss1 mRNA variants in Hatano rats
Yasuyuki HORII1,2, Sundun L. DALPATADU3,Tomoko SAGA3, Ryo OHTA,
Gen WATANABE1,2, Kazuyoshi TAYA1,2, Ishwar S. PARHAR3
General and Comparative Endocrinology, 2013 ; 181 : 246 -253
Differences in reproductive endocrinology distinguish Hatano high-avoidance animals (HAA) from
low-avoidance animals (LAA). Compared to HAA rats, female LAA rats secrete low levels of basal
luteinizing hormone (LH) and a reduced LH surge. To investigate the underlying cause of the differences
between the two strains, levels of the following mRNAs were measured in the hypothalamus of intact
and ovariectomized (OVX) females treated with vehicle control or estradiol-17 β (E2): gonadotropinreleasing hormone (Gnrh), newly isolated rat kisspeptin (Kiss)1 mRNA variant- 1 (Kiss1V 1 ) andvariant-2 (Kiss1V2) and estrogen receptor (Er)α . In OVX-HAA rats, the levels of Gnrh mRNA in the
preoptic area (POA) 30 h after E2 treatment were significantly higher than in OVX-LAA rats. For HAA
rats, the levels of Kiss1V1 and Kiss1V2 mRNA in the anteroventral periventricular nucleus (AVPV)
were significantly higher in the E2-treated group than in the vehicle-treated group. In the arcuate
nucleus (Arc) of HAA rats, Kiss1V1 and Kiss1V2 expression was significantly lower in E2-treatedfemales compared to vehicle-treated females. Kiss1V2 expression was significantly higher than Kiss1V1
expression in intact HAA rats. In E2-treated OVX-LAA rats, there were no changes in the expression
levels of Gnrh, Kiss1V1 or Kiss1V2. In intact LAA rats, no differences were observed in the expression
levels of Kiss1V1 or Kiss1V2 in the AVPV, but the expression levels of these mRNAs in the Arc weresignificantly lower in E2-treated OVX-LAA rats. Additionally, no strain differences were observed forErα mRNA expression in either the AVPV or Arc. These results indicate that the failure of estrogenic
regulation of GnRH neurons in the POA and of kisspeptin neurons in the AVPV of LAA rats causes low
LH secretion and reduced reproductive function.
1

The United Graduate School of Veterinary Sciences, Gifu University; 2 Laboratory of Veterinary

Physiology, Tokyo University of Agriculture and Technology; 3 Brain Research Institute, Schoolof Medicine and Health Sciences, Monash University Sunway Campus

分子生物学
オステオカルシン発現モニターマウスの作製とグルコサミンを用いた骨形成評価の一例
齊藤るみ子 , 谷口

真 1 , 中西友子 1 , 2 , 黒住誠司 3 , 高森吉守 3 , 佐藤建三 1 , 2

グルコサミン研究 , 2012 ; 8: 43- 50
オステオカルシン（osteocalcin 以下 , OC）は，骨の非コラーゲン性タンパク質の 25％を占めており，
骨組織のなかでも骨芽細胞において強く発現している．OC は骨の鉱質形成やカルシウムイオンの恒常性維持に寄与している．また，血清中の OC は骨形成マーカーとして用いられている．本研究では，OC
エンハンサー/ プロモーター領域とルシフェラーゼ遺伝子をつなぎ，in vivo イメージングにより OC 発現をモニターできるトランスジェニックマウスを作製し，D- グルコサミン塩酸塩（以下，GlcN）および Nアセチル -D- グルコサミン（以下，GlcNAc）
が骨形成に与える影響を検討した．
実験に先立ち，作製したトランスジェニックマウスが OC 発現をモニターできるかどうかを OC の発現を上昇させることが知られている活性型ビタミン D を用いて検討した．OC プロモーター活性が上昇したことから，作製した本マウスは骨形成の評価に利用できることを確認した．
続いて，各種 GlcN を用いた検討を行った．GlcN および GlcNAc の 4 日間短期投与（10％水溶液，強制23

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秦野研究所年報 Vol. 36. 2013

経口投与）では，OC プロモーター活性に差はなく，骨形成に与える影響は認められなかった．次に，28
日間長期投与（0.1％水溶液，混水投与）では，GlcNAc では変化がなかったものの，GlcN では投与後 1週間から OC プロモーター活性の上昇が認められ，投与終了まで持続した．このことから，GlcN の継続的な摂取は，骨形成能に一定の効果がある可能性が示された．
1

鳥取大学医学部生命科学科分子生物学分野 ; 2 鳥取大学染色体工学研究センター;

3

甲陽ケミカル株式会社

In vivo determination of vitamin D function using transgenic mice carrying a human osteocalcin
luciferase reporter gene
Tomoko NAKANISHI1,2, Rumiko SAITO, Makoto TANIGUCHI1, Haruka ODA1, Atsumi SOMA1,
Mayu YASUNAGA1, Mariko YAMANE1, Kenzo SATO1,2
BioMed Research International, 2013; Article ID 895706
Vitamin D is an essential factor for ossification, and its deficiency causes rickets. Osteocalcin,
which is a noncollagenous protein found in bone matrix and involved in mineralization and calcium
ion homeostasis, is one of the major bone morphogenetic markers and is used in the evaluation of
osteoblast maturation and osteogenic activation. We established transgenic mouse line expressing
luciferase under the control of a 10 -kb osteocalcin enhancer/promoter sequence. Using thesetransgenic mice, we evaluated the active forms of vitamins D 2 and D 3 for their bone morphogenetic
function by in vivo bioluminescence. As the result, strong activity for ossification was observed with
1α ,25-hydroxyvitamin D3. Our mouse system can offer a feasible detection method for assessmentof osteogenic activity in the development of functional foods and medicines by noninvasive screening.
1

Division of Molecular Biology, School of Life Sciences, Faculty of Medicine, Tottori University;

2

Chromosome Engineering Research Center, Tottori University

学会発表等

免疫毒性学
免疫毒性研究の温故知新−免疫毒性学会の発足経過と 20 周年への提言
大沢基保
第 19 回日本免疫毒性学会学術大会 2012 . 9 .15～9. 16（東京）
同会講演要旨集 , pp. 34 -36

毒性病理学
第 19 回技術研修会（アンケート・質問事項・グループミーティング）
報告
前田圭子 1 , 島田美千代 2 , 萩原 孝 3 , 山口 肇 , 五十嵐功 4 , 国遠かおり 5 , 位坂清継 6 , 三好貴子 7 , 中野健二 8
実験病理組織技術研究会・第 19 回総会・学術集会 2012. 6 . 22～6. 23（東京）
同会講演要旨集 , p. 14
1住友化学株式会社生物環境科学研究所; 2 エーザイ株式会社筑波研究所; 3 食品農医薬品安全性評価センター;

4

第一三共株式会社安全性研究所 ; 5 大日本住友製薬株式会社安全性研究所 ;6

扶桑薬品工業株式会社研究開発センター; 7 塩野義製薬株式会社新薬研究所 ;8

アステラスリサーチテクノロジー株式会社安全性研究部

24

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研究業績

ウサギにおける脳内埋植による局所的影響
今野和則 , 松田浩典 , 斉藤義明 , 臼見憲司 , 野口

聡 , 千坂亜希子 , 太田

亮 , 桑形麻樹子

第 39 回日本毒性学会学術年会 2012. 7. 17～7 . 19
（仙台）
Journal of Toxicological Sciences, 2012 ; 37 (Suppl. I): S254
粒子径の異なるナノ白金のラット経皮投与による皮膚病変の違い
熊谷文明 , 臼見憲司 , 丸茂秀樹 , 今野和則 , 吉岡靖雄 1 , 堤

康央 1 , 斉藤義明 , 桑形麻樹子

第 29 回日本毒性病理学会学術集会 2013. 1. 31～2. 1（つくば）
同会講演要旨集 , p. 96
1

大阪大学大学院薬学研究科毒性学分野

第 18 回技術研修会（関東部会），免疫組織化学染色のグループミーティングのまとめ紹介山口肇

実験病理組織技術研究会・第 20 回技術研修会 2013. 2 . 15
（大阪）
同会要旨集 , p. 2

一般毒性学
Wistar Hannover ラットの一般毒性試験における背景データ収集− SD ラットとの比較（4 施設共同）
三村雄一 1 , 柴田誠司 1 , 久田

茂 1 , 児玉晃孝 2 , 吉田正尚 2 , 増山

桑形麻樹子 , 早川和宏 3 , 4 , 青木豊彦 3 , 細川暁3, 牧

剛 2 , 成田隆博 2 , 立花滋博 , 古谷真美 ,栄二 5

第 39 回日本毒性学会学術年会 2012 . 7 . 17～7. 19（仙台）
Journal of Toxicological Sciences, 2012 ; 37 (Suppl. I): S1781

あすか製薬株式会社 ; 2 味の素製薬株式会社 ; 3 エーザイ株式会社 ; 4 株式会社サンプラネット ;5安全性試験コンサルタント

Wistar Hannover ラットにおける 4 , 4 '- チオビス
（6 -tert- ブチル -m- クレゾール）の長期投与による影響
立花滋博 , 古谷真美 , 加藤博康 , 根倉司 , 高岡裕 , 田面喜之 , 関

剛幸 , 堀内伸二 , 稲田浩子 ,三枝克彦 , 渡辺卓穂 , 桑形麻樹子
第 39 回日本毒性学会学術年会 2012. 7. 17～7. 19（仙台）
Journal of Toxicological Sciences, 2012 ; 37 (Suppl. I): S179
サブナノ白金およびナノ白金の経皮投与による毒性学的影響
桑形麻樹子 , 松本亜紀 , 熊谷文明 , 斉藤義明 , 丸茂秀樹 , 野口
関聡 , 臼見憲司 , 千坂亜希子 , 古谷真美 ,剛幸 , 加藤博康 , 高島宏昌 , 吉田徳幸 , 吉川友章 , 吉岡靖雄 1 , 堤
1

1

康央 1

第 39 回日本毒性学会学術年会 2012 . 7. 17～7. 19（仙台）Journal of Toxicological Sciences, 2012; 37 (Suppl. I): S2261大阪大学大学院薬学研究科毒性学分野

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秦野研究所年報 Vol. 36. 2013

生殖・発生毒性学
合成エストロゲン剤のマウス胎盤傷害性と胚致死作用
長尾哲二 1 , 加川

尚 1 , 斉藤義明 , 駒田致和 2

第 52 回日本先天異常学会学術集会 2012. 7. 6～7 . 8（東京）
同会プログラム・要旨集 , p. 99
1

近畿大学理工学部生命科学科 ; 2 徳島大学大学院ヘルスバイオサイエンス研究部

抗てんかん薬フェニトイン投与による SD ラット胎児脳発達への影響
瀬沼美華 , 高島宏昌 1 , 太田亮, 森

千里 2 , 小川哲郎 3 , 桑形麻樹子

第 52 回日本先天異常学会学術集会 2012 . 7. 6～7. 8（東京）
同会プログラム・要旨集 , p. 109
1

株式会社イナリサーチ試験管理部 ; 2 千葉大学大学院医学研究院環境生命医学 ;3昭和大学医学部第一解剖学

Wistar Hannover ラットの胚・胎児発生試験における背景データ収集− SD ラットとの比較（6 施設共同）
則武健一 1 , 池田高志 2 , 伊藤圭一 3 , 三輪洋司 4 , 瀬沼美華 , 高島宏昌 5 , 立石大志 6 , 久田

茂2, 牧

栄二 7

第 39 回日本毒性学会学術年会 2012 . 7. 17～7. 19（仙台）
Journal of Toxicological Sciences, 2012 ; 37 (Suppl. I): S183
1

第一三共株式会社 ; 2 あすか製薬株式会社 ; 3 公益財団法人食品農医薬品安全性評価センター;

4

株式会社日本バイオリサーチセンター; 5 株式会社イナリサーチ ; 6 株式会社新日本科学 ;7

安全性試験コンサルタント

ラット胎生期ヒ素暴露の胎児脳発達への影響 : セロトニン神経発生への影響
瀬沼美華 , 古谷真美 , 高島宏昌 , 太田亮, 森

千里 1 , 小川哲郎 2 , 桑形麻樹子

第 39 回日本毒性学会学術年会 2012 . 7 . 17～7. 19（仙台）
Journal of Toxicological Sciences, 2012 ; 37 (Suppl. I): S1911

千葉大学大学院医学研究院環境生命医学 ; 2 昭和大学医学部第一解剖学

Biological safety evaluation of electrostatic atomized water using tests for genotoxicity
and reproductive toxicity
Ryo OHTA, Yuzuki NAKAGAWA
Nano - Symposium“Application and Environmental Health and Safety Implications of Engineered
Nanomaterials and Nanotechnology”2012 . 9. 24（京都）
同会 Abstract Book

細胞毒性学
Bhas 42 cell transformation assay for the prediction of chemical carcinogenicity
Ayako SAKAI, Kiyoshi SASAKI, Noriho TANAKA
2012 World Congress on In Vitro Biology 2012 . 6 . 3～6. 7（Bellevue, USA）
In Vitro, 2012; 48 (Abstract): S16

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研究業績

Bhas 42 細胞形質転換試験における 6 - ウェル法と 96 - ウェル法の同等性―国際バリデーション研究の結果から―酒井綾子 , 佐々木澄志 , 遠藤伸子 , 山崎晶次郎 , 梅田

誠 , 田中憲穂

日本動物実験代替法学会第 25 回大会 2012 . 12 . 7～12 . 9（東京）
同会プログラム・講演要旨集 , p. 176

遺伝毒性学
放射線照射によるトリグリセリド分解生成物（2 - アルキルシクロブタノン類）の遺伝毒性および発がん性山影康次 , 高橋俊孝 , 生悦住茉友 , 須井哉 , 川上久美子 , 松本浩孝 , 豊泉友康 , 根岸沙記 , 古田雅一 1

日本環境変異原学会第 41 回大会 2012. 11. 29～11. 30（静岡）同会プログラム・要旨集 , p. 94
1

大阪府立大学地域連携研究機構・放射線研究センター

カーボンナノチューブの CHL/IU 培養細胞を用いた染色体異常試験（その 2）
高橋俊孝 , 中川ゆづき , 豊泉友康 , 田島恵理 , 西村哲治 1 , 本間正充 2 , 山影康次
日本環境変異原学会第 41 回大会 2012 . 11 . 29～11 . 30
（静岡）同会プログラム・要旨集 , p. 105
1

帝京平成大学 ; 2 国立医薬品食品衛生研究所

ヒト 3 次元表皮モデルを用いるアルカリコメットアッセイの検討
豊泉友康 , 須井哉 , 渡辺美香 , 中川ゆづき , 山影康次

日本環境変異原学会第 41 回大会 2012 . 11. 29～11. 30（静岡）同会プログラム・要旨集 , p. 135
ハイ・スループット微生物遺伝毒性試験法の検討 8
須井

哉 , 川上久美子 , 根岸沙記 , 山田雅巳 1

日本環境変異原学会第 41 回大会 2012. 11. 29～11. 30（静岡）同会プログラム・要旨集 , p. 137
1

国立医薬品食品衛生研究所

化合物チオアセトアミドを用いた反復投与による肝臓小核試験法の有用性の検討：
MMS 共同研究の個別報告
松本浩孝 , 須井哉 , 涌生ゆみ 1 , 川迫一史１

日本環境変異原学会第 41 回大会 2012. 11. 29～11. 30（静岡）同会プログラム・要旨集 , p. 152
1

三菱化学メディエンス株式会社

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食品衛生学
HILIC-MS/MS による粉ミルク中ヌクレオチド・ヌクレオシドの一斉分析法
小原路得子 , 渡辺卓穂
第 104 回日本食品衛生学会 2012 .9 . 20～9. 22（岡山）
同会講演要旨 , p. 69
食品衛生外部精度管理用調査試料の作製検討−残留動物用医薬品検査用調査試料編−
高坂典子 , 勝村利恵子 , 福光

徹 , 鈴木達也 , 渡辺卓穂 , 小島幸一

日本薬学会第 133 年会 2013. 3 .27～3. 30（横浜）
同会要旨集 , p. 252

動物実験代替法
培養角膜モデル LabCyte CORNEA-MODEL 24 を用いた眼刺激性試験代替法共同研究
小島肇 1 , 安中梶田明美 8 , 中村

希 2 , 土屋成一郎 3 , 吉武裕一郎 4 , 許
牧 9 , 渡辺美香 , 中嶋

叡 5 , 鈴木克 6 , 嶋谷亘7,

圓 10 , 坂本興嗣 11 , 竹田竜嗣 12 , 久間將義 13 ,池田英史 14 , 稲垣愛美 15 , 棟近由記美 16 , 山本

裕 17 , 笠原利彦 18 , 福田隆之 19 , 仲原

聡 20 ,

渡辺真一 21 , 倉田隼人 22 , 篠田伸介 23 , 加藤雅一 24
日本動物実験代替法学会第 25 回大会 2012. 12 . 7～12 . 9（東京）同会プログラム・講演要旨集 , p. 137
1

国立医薬品食品衛生研究所 ; 2 株式会社アイビー化粧品 ; 3 石原産業株式会社 ;4

オッペン化粧品株式会社 ; 5 花王株式会社 ; 6 一般財団法人化学物質評価研究機構 ;7

株式会社化合物安全性研究所 ; 8 株式会社鎌倉テクノサイエンス ; 9 小林製薬株式会社 ;10

公益財団法人食品農医薬品安全性評価センター; 11 大正製薬株式会社 ; 12 DRC 株式会社 ;13

東洋ビューティ株式会社 ; 14 日本コルマー株式会社 ; 15 財団法人日本食品分析センター;

16

日本農薬株式会社 ; 17 株式会社ノエビア ; 18 富士フイルム株式会社 ;19

株式会社ボゾリサーチセンター; 20 株式会社マンダム ; 21 ライオン株式会社 ;22

ロート製薬株式会社 ; 23 株式会社薬物安全性試験センター;

24

株式会社ジャパン・ティッシュ・エンジニアリング

IL-8 Luc assay の施設間差試験− Phase I, Phase IIa の結果ならびに今後の展望−木村

裕 1 , 渡辺美香 , 齊藤るみ子 , 鈴木紀之 2 , 岩城知子 3 , 金子渡辺

文 4 , 山影康次 , 斎藤幸一 2 , 中島芳浩 3 , 近江谷克裕 5 , 酒井綾子 , 大森

小島

肇 6 , 田中憲穂 , 相場節也 1

愛 4 , 高田めぐみ 4 , 田中裕美 4 ,
崇 4 , 山崎晶次郎 ,日本動物実験代替法学会第 25 回大会 2012 . 12. 7～12. 9（東京）同会プログラム・講演要旨集 , p. 145
1

東北大学大学院医学系研究科皮膚科学講座 ; 2 住友化学株式会社生物環境科学研究所 ;3

独立行政法人産業技術総合研究所・健康工学研究部門 ; 4 同志社大学 ;5

独立行政法人産業技術総合研究所・バイオメディカル研究部門 ; 6 国立医薬品食品衛生研究所

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研究業績

LabCyte EPI-Model を用いた JIS L 1918 繊維製品の皮膚一次刺激試験
渡辺美香 , 小林美和子 , 生悦住茉友 , 山影康次
日本動物実験代替法学会第 25 回大会 2012. 12. 7～12 . 9（東京）同会プログラム・講演要旨集 , p. 155
眼刺激性試験代替法である STE 試験の香粧品製品を用いた施設間再現性
安保孝幸 1 , 渡辺美香 , A. HILBERER 2 , A. HEPPENHEIMER 3 , 大島健一 4 , D. CAMERON 5 ,A. KIRST 6 , 額田祐子 1 , 坂口斉 1 , 西山直宏 1

日本動物実験代替法学会第 25 回大会 2012. 12 . 7～12 . 9（東京）同会プログラム・講演要旨集 , p. 160
1

花王株式会社 ; 2 Institute for In Vitro Sciences, Inc.; 3 Harlan Cytotest Cell Research GmbH;4

株式会社カネボウ化粧品 ; 5 Kao USA Inc.; 6 Kao Germany GmbHSIRC-CVS 試験を用いた眼刺激性評価代替法の国際バリデーション研究（I）
簾内桃子 1 , 福田隆之 2 , 池田英史 3 , 鄭美淑 4 , 大森 崇 5 , 田中裕美 5 , 山影康次 , 萩野滋延 6 , 小島肇1

日本動物実験代替法学会第 25 回大会 2012 . 12. 7～12. 9（東京）同会プログラム・講演要旨集 , p. 163
1

国立医薬品食品衛生研究所 ; 2 株式会社ボゾリサーチセンター東京研究所 ;3

日本コルマー株式会社研究開発本部 ; 4 株式会社バイオトクステック ;5同志社大学文化情報学部 ; 6 株式会社資生堂リサーチセンター

Collaboration study on eye irritation alternative method with human corneal mode;
Labcyte Cornea-Model24
H. KOJIMA1,2, N. ANNAKA2, S. TSUCHIYA2, Y. YOSHITAKE2, R. XU2, M. SUZUKI2, W. SHIMATANI2,
A. KAJITA2, M. NAKAMURA2, M. WATANABE, M. NAKAJIMA2, K. SAKAMOTO2, R. TAKEDA2,
M. HISAMA2, H. IKEDA2, A. INAGAKI2, Y. MUNECHIKA2, Y. YAMAMOTO2, T. KASAHARA2,
T. FUKUDA2, S. NAKAHARA2, S. WATANABE2, H. KURATA2, S. SHINODA2, M. KATOH2,3
52nd Society of Toxicology Annual Meeting 2013. 3. 10～3. 14（San Antonio, USA）
Toxicologist, 2013: 208
1

National Institute of Health Sciences; 2 Japanese Society for Alternative to Animal Experiments;

3

Japan Tissue Engineering Co., Ltd.

The interlaboratory reproducibility of the STE test for assessing eye irritation of
cosmetic products
Y. NUKADA1, T. ABO1, A. HILBERER2, A. HEPPENHEIMER3, M. WATANABE, K. OOSHIMA4,
D. CAMERON5, A. KIRST6, H. SAKAGUCHI1, N. NISHIYAMA1
52nd Society of Toxicology Annual Meeting 2013 . 3 . 10～3. 14（San Antonio, USA）
Toxicologist, 2013 : 208
1

Kao Corporation; 2 Institute for In Vitro Sciences, Inc.; 3 Harlan Cytotest Cell Research GmbH;4

Kanebo Cosmetics, Inc.; 5 Kao USA Inc.; 6 Kao Germany GmbH29

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秦野研究所年報 Vol. 36. 2013

食品機能学
菜種（カノーラ）
油摂取が脳卒中易発症高血圧自然発症ラット（SHRSP）の病態悪化を促進する機序
小野田早苗 1 , 内藤由紀子 2 , 立花滋博 , 河村さやか 1 , 大原直樹 1 , 吉川真衣 1 , 新美まどか 1 , 川口真帆 1 ,
宮澤大介 1 , 安井裕子 1 , 山田和代 1 , 奥山治美 1
第 39 回日本毒性学会学術年会 2012 . 7 . 17～7. 19（仙台）
Journal of Toxicological Sciences, 2012 ; 37 (Suppl. I): S217
1

金城学院大学薬学部 ; 2 国立循環器病研究センター

中期多臓器発癌試験法によるアラキドン酸の発癌プロモーション作用への影響評価
立花滋博 , 斉藤義明 , 青木聡子 , 安藤栄里子 , 立松憲次郎 1 , 大原直樹 2 , 永田伴子
日本脂質栄養学会第 21 回大会 2012 . 9 . 7～9. 8（相模原）
Journal of Lipid Nutrition, 2012; 21 ( 2 ): 1481

岐阜薬科大学放射化学研究室 ; 2 金城学院大学薬学部

DSS 誘導ラット大腸炎に対するアラキドン酸補給の影響
内藤由紀子 1 , 遠藤恒介 1 , 紀

旭1, 馬嘯 1 , 立花滋博 , 安藤栄里子 , 青木聡子 , 永田伴子 , 宮澤大介 2 ,岩井直温 1
日本脂質栄養学会第 21 回大会 2012 . 9 . 7～9. 8（相模原）
Journal of Lipid Nutrition, 2012 ; 21 ( 2 ): 205
1

国立循環器病研究センター病態ゲノム医学部 ; 2 金城学院大学薬学部

発達神経毒性学
バルプロ酸の胎生期曝露により実験動物に誘発される発達神経毒性
小川哲郎 1 , 塩田清二 1 , 桑形麻樹子
第 52 回日本先天異常学会学術集会 2012 . 7 . 6～7. 8（東京）
同会プログラム・要旨集 , p. 67
1

昭和大学医学部第一解剖学教室

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