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1 JEMS/BMS
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4 2 N H C C C NH 2 Furylfuramide (AF-2)
5 Dibenzo[a, l ]pyrene ( DBP) PAH
6 Mutant Frequencies of lacz and cii gene Induced by DBP and AF cii lacz cii lacz Liver 6 mg/kg 120 mg/kg AF-2 DBP Control Forestomach Colon Spleen
7 AF2 Bacteria specific mutagen TA1535,1538 aflatoxin B1, B[a]P, DMBA AF2
8 sensitivity)
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16 sensitivity)???
17 Food Additives Tested in NTP Rodent Bioassay and Their Results of the Ames Test Carcinogenicity 3 Mutagenicity from How Many Food Additives Are Rodent Carcinogens? F.M. Johnson, Env. Mol. Mutagen. 39, (2002)
18 Effect of Administration Route on Rodent Carcinogenicity Noncarcinogens Carcinogens
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22 TRENDS in Pharmacological Sciences Vol. 22 No.6 June 2001 Key challemges for toxicologists in the 21st century Lewis L. Smith Syngenta CTL, Alderley Park, Macclesfield, Cheshire, UK
23 Much of the safety evaluation of drugs and chemicals involves administration of a large dose of the compound to a small number of animals to characterize the effect, followed by the extrapolation of this to a large number of people exposed to a small dose of the compound.
24 Safety factor Safety factor 10 for interindividual variation (SNPs) Safety factor 10 for human might be more sensitive Safety factor 10 for safety reason in some cases At least 100 and sometimes 1000 is applied 1000
25 DDT 2,2-bis(p-chlorophenyl) -1,1,1-trichloroethane DDT had saved ~50 million lives and averted more than 1 billion illness It was found, at high doses, to increase liver tumors in mice Public concerns over the environmental effects were enhanced by the publication of Silent Spring in Sweden 1970, USA 1972, Japan 1972 WH South Africa 4117 ( 95) )
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30 Natural mutagen
31 Ames -1 1ppm DDT PCB EDB
32 Ames
33 Ames -3
34 Aristolochic acid CH N 2 C N C NH R R R 1 AAI ;R=H 2 3 CH AAII;R=CH 3 N 2 Structure of aristolochic acid I (AAI ;R=CH 3 ) and aristolochic acid II (AAII;R=H). R R N R NH (Aristolochia fangchi) N N N N HN C NH 4 (da-n 6 -AA) 5 N N N H HN C (dg-n 2 -AA) Chinese herb nephropathy
35 1500 Aristrochic acid (lacz) Aristolochic acid (lacz) (cii) Aristolochic acid (cii) (x 10-6 ) 0 CH N 2 R Aristolochic acid
36 Environmental Pollution, Pesticides, and the Prevention of Cancer: Misconceptions BRUCE N. AMES AND LIS SWIRSKY GLD FASEB J. Vol 11, (1997) #1 #2 #3 #4
37 #5 #6 #7 #8 #9
38 Ames
39 Hazard Identification Risk assessment
40 (1) 2.25pg/kgbw/ pgTEQ/kgbw/ )
41 (2002) #1 #2 #3non-genotoxic carcinogen #4
42 #5 #6 #7 #8 #9
43 in vito in vivo bacteria yeast mammalian human ( DNA ( transgene endogene vs
44 NR Forward mutation
45 Positive rate
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47 Top 10 micronucleus-inducing chemicals in 100 IARC carcinogens (Groups 1, 2A and 2B) Rank Chemicals Dose (mg/kg) Max MN Groups Antineoplastic 1 Diepoxybutane B 2 Cisplatin A * 3 Melphalan * 4 Dacarbazine B * 5 N-methyl-N-nitrosourea A 6 Daunomycin B * 7 4-Aminobiphenyl Chlorambucil * 9 2-Methylaziridine B 10 1,3-Propane sultone B Data from Evaluation of the rodent micronucleus assay in the screening of IARC carcinogens (groups 1, 2A and 2B) The summary report of the 6th collaborative study by CSGMT/JEMS MMS. Mutation Res. 389, (1997)
48 DNA Genomics, Proteomics, Metabonomics
49 Hazard Identification Risk Evaluation SNPs Mutagenomics, Mutaproteomics, Mutametabolomics, IT population Germ Cell Mutagenesis,
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Jpn. J. Health Phys., 52 (2) 55 60 (2017) DOI: 10.5453/jhps.52.55 * 1 * 2 * 2 * 3 * 3 2016 10 28 2017 3 8 Enhancement of Knowledge on Radiation Risk Yukihiko KASAI,* 1 Hiromi KUDO,* 2 Masahiro HOSODA,*
Movement of Population and Structure of 'Buraku' in the Edo Period Akira FUKUYAMA Section of Economics, Osaka Kyoiku University, Kashiwara, Osaka 582, Japan That goes without saying now, historical study
CAS NC(CH 2 ) 4 CN 1,4- C 6 H 8 N c.c d = Pa
1 200117 21512 CAS 111693 110 NC(CH 2 ) 4 CN 1,4- C 6 H 8 N 2 108.14 1 99 2-1. 2 1 295 159 c.c. 550 3 1.7-4.9 20 d 0.965 4 3.73 = 1 0.3 Pa 0.002 mmhg20 2 log Pow-0.32 m/z 41, 1.0 68 0.54 54 0.43 4 Koc9-16
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1 967 2482 CAS 50000 CH 2 O 30.03 2952% 12.5 % 1. 2) -92 2) -19.5 2) 5085 3) 424 3) 7.073.0% 4) 20 d 4 0.815 5) 1.03 ( = 1) 5) 1.33 kpa (10 mmhg) (-88.0) 2) log Pow0.35 ( ) 6) 0.35 ( ) 7) 1) m/z 29 ( 1.0
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1 20019 1527 CAS 1317368 1230 PbO 223.20 1 99 1. 2 888 2 9.53 0.017 g/l 20 3 3 2 2. 10 29,309 t 22,069 t 7,240 t 4 1 3. 1 2 3.5 6 1 µg/l 9.1-24 2 µg/l < 43 6 27,431-70,000 4.5-1,300 13.4-17 31.7 0.48-3,459
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This report shows innovation of competency of our faculty of social welfare. The aim of evaluation competency is improvement in the Social welfare education effects, by understanding of studentʼs development
;~ (Summary) The Study on the Effects of Foot Bathing on Urination Kumiko Toyoda School of Human Nursing, University of Shiga Prefecture Background Foot bathing is one of the important nursing care for
coccus aureus Corynebacterium sp, Haemophilus parainfluenzae Klebsiella pneumoniae Pseudornonas aeruginosa Pseudomonas sp., Xanthomonas maltophilia, F
VOL.43 S-1 coccus aureus Corynebacterium sp, Haemophilus parainfluenzae Klebsiella pneumoniae Pseudornonas aeruginosa Pseudomonas sp., Xanthomonas maltophilia, Flavobacter- Table 1. Concentration of grepafloxacin
CAS H 3 C C CH 2 C 9 H tert d = hpa
1 200140 35 CAS 98839 1335-2- H 3 C C CH 2 C 9 H 10 118.18 1 99 4-tert- 1. 2-23.2 2 163164 2 54 574 3 0.96.6 20 d 4 0.9082 2 4.07 = 1 2.5 hpa 1.9 mmhg20 2 4 log Pow3.48 3.44 m/z 118, 1.0 103 0.58 91 0.21
The New ICH Guideline on Genotoxicity (S2)
ICH S2 の概要および遺伝毒性研究に おける発がん性の意味 本間正充 国立医薬品食品衛生研究所 変異遺伝部 TOPICS ICH S2(R1) ガイドライン ( 案 ) のポイント 他のガイドラインや研究分野への影響 遺伝毒性発がん物質のリスク評価と管理 The International Conference on Harmonisation of Technical Requirements
t 492 t mg/l 30 mg/l BOD 95 OH = cm 3 / sec 25 8 OH /cm 3 12 = ph ph
2-1 200169 2740 CAS 110-49-6 1103 2- O H 3 C C O CH 2 CH 2 O CH 3 C 5 H 10 O 3 118.13 200168 2-1 99 2-1. 2 2, 3-65 2, 3 144145 45 o.c. 3 392 3 1.512.3 d19 1.009 2 4.07 = 1 30 Pa 0.23 mmhg20 2 4 log Pow0.10
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Fig. 1 Chemical structure of TE-031 Code number: TE-031 Chemical name: (-) (3R, 4S, 5S, 6R, 7R, 9R, 11R, 12R, 13S, 14R)-4-[(2, 6-dideoxy-3-C-methyl-3-
Fig. 1 Chemical structure of TE-031 Code number: TE-031 Chemical name: (-) (3R, 4S, 5S, 6R, 7R, 9R, 11R, 12R, 13S, 14R)-4-[(2, 6-dideoxy-3-C-methyl-3-O-methyl-a-L-ribo-hexopyranosyl) oxy]-14-ethyl-12,
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2-1 9628 31307 CAS 117817 2- O C O * DOP* DEHP 2- C O O * n- C 24 H 38 O 4 390.56 CH 2 CH 2 CH 2 CH 3 CH (CH 2 ) 3 1 99 % 2- ABHT 1. 2-55 3 3, 4 386 171 350 6 0.1 % d 20 4 0.9861 4 13.48 0.30410-4 Pa 2.2810-7
CHEMOTHERAPY Fig. 1 Body weight changes of pregnant mice treated orally with AM- 715 Day of sestation
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VOL. 36 S-3 CHEMOTHERAPY 437 438 CHEMOTHERAPY JULY 1988 Fig. 1 Contractile response of gastrointestinal tract to intravenous administration of saline and EM in interdigestive state in dogs (a) : Saline,
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