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1 JEMS/BMS
2
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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,*
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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 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
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