Document JJBj9JKaEb5eBG4Be02VxwMn6

ARR -- 3266 3 : AR2AG _326 7 REPORT ON MUTAGENICITY TEST RESULTS USING MICROORGANISMS I ] Nomenclature of novel N 1 chemical substance (by a ag win TUPAC nomenclature) [Oername 1 Structure or empirical | not certain) L_8 | A Fl Pmoam roc |7 [|1 sLoetmNoi.ovfineovnee | _--Y foa n. -- " cam =| usedint|es Ret m | CAS No. T sppessncontmom | on M"Moelletciunlgaproiwnetight [Boiting point [pm EE TT IE" Stability 134455293 |Vaporp| ress--wre| T 570-37 |Distribution coefficient | = |1 = empersre | Brown viscous solid [ Unknown | [5oes -------- | water | <50 mg/mL' 1 = 4 Other (*3) *3 s | Ra Nu, *3 Ethanol soluble (solubility unknown) p*r4ep5a0ra-tmigon/,mtLhssusjpuedngseidonstsahbloewecdonnfoidrimsecdoloosrattieon,ahFeiattsemWiosrskiso)n, etc., up to 2 h after ) | | 64746 Company Senitized. Doss nol contain TSCA Cl 2 --_ [ote:nopages 2 and 3] 6. Minimum glucose agar plate medium Selfmade or acqui.red | 1. Self-made poqired (producer. Oriental Kobo Kogyo KK) Lofot racqN uiredo specimen| November 8, 2002 ANI4OKR | `Name of agar used, `manufacturer, Lot No. 7. Testing method (1) Testing metanhdroeasdon fotrs selection Reasons for selection in the caseof Other"| _-- | (2) Testing conditions --_ postion Na phosphate buffer solution (in direct method) [| moubasion | oan =-- Tempers 37205C 305C 8. Colony counting method Manual None _@ Instrumental 2. Yes (correction method: area and number drop) Pin ci) 9. Test results (1) Test results are shown in a separate table: (2) Evaluation of results Reasons for evaluation muRteagtairodnlceoslsoonifetshewaprselseesnsctehoarn a2btsiemnecseotfhe$n9egmaitxi,veagcaoinntsrotla,llthbuacstmeruitaa,getnheicniutmybwearsojfudbagcekd-to be negative. ~~ aris DompernySanta.Bonsnot oontain vac mmr --_ (3) Notes Dosage setting `With a maximum of 5000 ng/mL, an overall 6-step dosage was set with a nominal dilution ratioof4. Dosage setting experiment-2 As a result of dosage setting experiment-1, regardlessofthe S9 mix, growth inhibition was realized against all test bacteria. More than 4 doses for the effective dosage showing no `growth inhibition could not be obtained with TA100, TA1S35, and TALS37 in the absence of the $9 mix. For the dosage-setting experiment evaluation and dosage setting of this test with the effective dosage established, with a maximum dosage of 313 ng/plate showing growth inhibition, 6-step dosagewasset at a nominal dilution ratio of4. `Main test `From the dosage-setting experiment results, with the maximum dosage showing growth inhibition, in the absence of the S9 mix, the 313-pg/plate for TA100, TA1535, and TAI537, and the 1250-ug/plate for WP2 uvrA and TAS, the 6-step dosage was set with a nominal dilutionratio of 2. Inthe presence of the S9 mix, the total [overall]6-step.dosage was set with nominal dilution ratio o2f at the most with the 1250-g/plate for TA100, TALS35, and 7 `TA1537 and the 5000-pg/plate for WP2 uvrA and TA9S. + Growth inhibition was observed at a dosage above 156 ug/plate for TA100, above 313 ng/plate for TA535 and TAL537, and above 1250 pg/plate for WP2 uvrA and TA9; in the absenceof S9 mix, and above 1250 ug/plate for TA100, TA1535, and TA1537 and 5000 ng/plate for WP2 uvrA and TA98 in the presence of $9 mix. No precipitation of the test substance occurred. Numberofback-mutation colonies of the negative control and positive control was within the historical data range. No staining in test system occurred, indicating that the testing was a 10. Others. =0973(24)7211 FAX: 0973(23)9800 [ nieser[P`ad nd name e | Testing DDepaarrttmmeenntt33. ________ShSohozzooOOggurraa_| [[Bperence | alyews | KO01-2869 2/4/03 toee 3/5/03 . --_ Test results (dosage setting experiment-1) Ebieen | Tare Test substance name} - [ow Tes So we emer] [os1 8 wl lt al Fal ul = Ere aE a ee| onBoalEonBon om] -- ve El e BowlEl w] ou 3 [oo me i |DosageGegplae) [----477Tw Tas17} [Notes] (: average valueofnumberofcoloniesofeach plate *: growth inhibitionofbacteria was observed. AF-2: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide: NaN: sodium azide ICR-191: 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridines2HCI 2AA: 2-aminoanthracene Pe sempessnm-- s PS Test results (dosage setting experiment2) Test substance name} Nsoetvaiionn | Testotem dose Soaloe) E% sl 06 qm] rT &fF 10 t ` om [ew [EEWg Lm195 TswltaT7l g L TM 9 w10e3 l 3 T 12 w10e]19 ~~ 533] vvii[tteM[oe[BmemecgeoesT[ 7-- #0 2 [0 wk 0| 8ip ] [Notes] (): average value of number ofcolonies of ach plate *: growth inhibition of bacteria was observed. AF-2:2.Q2-furyl)-3-5-nitro-2-fury acrylamide: NaN: sodium azide ICR-191: 2-methory-6-chloro-9-[3-(2-<hloroethyDaminopropylamino]acridines2HCL pons `Gompany Sanilized. Doss ot contain TSCA GE ` ~~ `Test results (main test) "Test substance name] Earn est substance ee = = [meoe [a = [hme "oan ER YI JP me el fw] Tame--T-- au-- T--a TT -- aa io [: = mhe|e 8 Tol BolBowlEa] [Notes] ():garvoewrtahgie v nia oonl fnofuu bmabce eterroifa was ses. colonies of each plate AF-2: 2-(2-furyl)-3-(5-nitro-2-furyDacrylamide NaNj: sodium azide --_ 2s0a4n:s 2aminosnircene CfompanySanita, Boos ckcain TRACE ICR-191: 2-methoxy-6-chloro-9-[3-(2-chloroethylJaminopropylaminoJacridines2HCI ' --_ Dosage-Reaction Curve (dosage seting experiment-1) No0.off back mutation Siins colonies/ppslate Sintwh ww o o wn ws-- ne an 0 won Test substance dosage (ug/plate) Figure 1: Dosage-reaction curve without S9 mix No. ofbackmutation SiJilm,s colonies/0plate SSiinfat - ; Bios . wn ws ne as = son Test substance dosage (ug/plate) Figure 2: Dosage-reaction curve with S9 mix --_ [ Company Senlizod Doss not contain Tso ca s -~. Dosage-Reaction Curve (dosage setting experiment-2) Ncool.onoifesbiapclka-tmeutation S9immms ww . . -- we t-- m em ws wa PA Test substance dosage (ug/plate) Figure 3: Dosage-reaction curve without S9 mix --~ --_ sas `CompanySenltized. Dossnot contain TSCA Cat  -- DosageReaction Curve (main test) No.ofbackmutation colonies/-plate 0a: is S viise o am ws mi oma om ow es ue Test substance dosage (ug/plate) Figure 4: Dosage-reaction curve without S9 mix ~~ No. of back-mutation colonies/plate 89:: SHiiotea w " . | \ o wa mi ow om ow me m0 sm | `Test substance dosage (ug/plate) Figure 5: Dosage-reaction curve with $9 mix --- || 64746 `Company Sanitzed. Does not containTSCACBI 0 --_ Kiatsu No. 90 February 22, 2001 Jiro Hiraishi Chairman, BoardofDirectors Kagakubusshitsu Heikakenkyukiko Labor Standards Bureau MinistryofHealth, Labor and Welfare: Safety-Health Law GLP Feasibility Confirmation of Test Facilities `This is notification of the followingjudgments of the title matter requested on March 24, 2000. Description 1 Name of test facilitesforfeasibility confirmation ~ Hita Works, Kagakubusshitsu Heikakenkyukiko 2 Title of test requiring feasibility confirmation Mutagenicity test using microorganisms and chromosomal aberration test using `mammalian cultured cells 3 Inspection date July 24, 2000 to July 25, 2000 4 Judgment Pass 5 Effective duration of feasibility confirmation July 26,2000to July 25, 2003 6 Notes None ~~ 4146 `Company Sanitized. Dossnotcontain TSCA CB u --_ STATEMENT TestRequester: Test Title: TestCodeNo: Dupont KX. Hita Works Kagakubusshitsu Heikakenkyukiko Mutagenicity test my. `microorganisms K01-2869 `The test described above was carried out in accordance with Standards for Facilites for `Toxicity Test (1988 Ministry of Labor Bulletin No. 76, partially amended on March 29, 2000), `Test Facilities Specified in Ministry Order Article 4: Defining Tests for New Chemical `Substances and Toxicity Test of Designated Chemical Substances (March 31, 1984, Kanhogyo No. 39, Yakuhatsu No. 229, 59 Kikyoku No. 85,amendedon March 1, 2000), and OECD. ~ PrinciplesofGood Laboratory Practice (November 26, 1997). `Yoshifumi Fujino Manager March 5, 2003 -- cris `CompanySanitzod.DossnotcontainTSCA Cat | 1| STATEMENT | Hita Works KagakubusshitsuHeikakenkyukiko | TestRequester: Dupont KK. | Test Tie: Mutagenicity test J -- microorganisms | | Test Code No.: K01-2869 effective`The test described above was carried out in accordance with Standards for Facilities for T"TeosxticFiatciylTietsiets(S1p9e8c8ifMiiendiisntrMyinoifsLtaryboOrrdBeulrlAerttiinclNeo.4;76D,efpianrtiinagllTyesatmsefnodreNdeown March 29, Chemical 2000), SubstancesandToxicity Test of Designated Chemical Substances (March 31, 1984, Kanhogyo No. 39, Yakuhatsu No. 229, 59 Kikyoku No. 85, amendedon March 1, 2000), and OECD ~~ Principles of Good Laboratory Practice (November 26, 1997). "The final report precisely reflects raw dats,and ii to confi the estdata as being Shozo Ogi Principal Tester March 5, 2003 --~ 64746 `CompanySanitized. Doesnotcontain TSCAcBY  - RELIABILITY WARRANTY Hita Works Kagakubusshitsu Heikakenkyukiko TestRequester: Dupont KK. TestTile: sei cooEY microorganisms TestCodeNo: KOI-2869 "This test has been audited or inspected by the QA DivisionofHita Works, Kagakubusshitsu Heikakenkyuiiko. Supervision or inspection dates and reporting cates to the principal tester and managemenret given below. Autiingorf:iopetion itfo Auditingor | Auditing or inspection inspectiondate result reportdate 2/5/2003 ~ 2/13/2003 Amendment of test plan document 21772003 `Amendment of test plan document (No.2 2192003 Recording andreport draft 2125/2003 5/2003 "The test described above was carried out in accordance with Standards for Facilites for Toxicity Test (September 1, 1988 Ministry of Labor Bulletin No. 76, partially amended on March 29, 2000), Test Facilities Specified in Ministry Order Arce 4: Defining Tests for New Chemical Substances and Toxicity Test of Designated Chemical Substances (March 31, 1984, Kanhogyo No. 39, Yakuhatsu No. 229, 59 Kikyoku No. 85, amended on March 1, 2000), and. `OECD Principles of Good Laboratory Practice (November 26, 1997) and in accordance with test methods defined in Toxicity Test Standards (Ministry ofLabor Baletin No. 7, September 1, 1988; MinistryofLabor Bulletin No. 67, June 2, 1997), Specific Procedure of Mutagenicity Test Using Microorganisms (February 8, 1999), Testing Methods for New Chernical Substances, saris Company Sanitized. Doss nol contain TSCA C8) 1 "~ partial amendment (Kanhogyo No. 700, Yakuhatsu No. 1039, 61 Kikyoku No. 1014, December 5, 1986; Kanhoan No. 287, Eisei No. 127, 1997-10-31 Kikyoku No. 2,October31, 1997) "This report accurately describes the testing method and procedure; the reported results accurately reflect raw data of the tests, March 5, 2003 Keiji Shiraishi Reliability Warranty Officer Yoshifumi Fujino Manager March 5, 2003 Language Services Unit Phoenix Translations January 13, 2004 --~ sands `Company Sanizad. Doesnotcontain TSCA Cal