Document Ra75OJbQVo6rJL8ar89EwaxBv

DownloadRandom document
n- edtor AR226-09FF Industrial 1B8I10OF-RTONETSATGELaRbOoAraDtonies, Ine. NORTHBROOK. ILLINOIS 60062 REPORT TO 3M COMPANY REVERSE MUTATION T-1485 STUDIES WITH IN OFINVEESSAALCMCOHNAELRLOACMESYSTRSATIRNASIANND P.O. NO. LP-003397-400 AUGUST 10, 197 o 1BT NO. 8540-09238 z= 320 2G 5iN Conizin NO 0B) 414 Y Industrial 1B 810 -I FRTOENO TSATGELzRbOoArDatovies, Dre, NORTHBROOK. ILLINOIS 60062 August 10, 1976 Dr. James E. Long Manager, Toxicology Services 3M Company 3M Center St. Paul, Minnesota 55101 Dear Dr. Long: Re: TB-T148N5o.in85F4i0v-e09S2a3l8mo-neRlelvaerStsreaiMnustaatnidonOSnteudSiaecschwiatrhomyces Strain = P.O. No. LP-003397-400 We are submitting herewith our laboratory report prepared in connection with the above study. Very truly yours, Jccibp J.C. Calandra President 2 9/5 | Industrial BIC TEST Laboratories, Jue REPORT TO 3M COMPANY REVERSE MUTATT1I4O8N5 STUDIES WITH IN OFINVEESSAACLCMHOANREOLMLYAGESSTRSATIRNASIANND P.0. NO. LP-003397-400 AUGUST 10, 197 IBT NO. 8540-09238 IL mirodsetion A sample identified as T-1485 was received from 3M Company for the purpose of conducting reverse mutation studies. The test material was evaluated for genetic activity in microbial assays with and without the addition of mammalian metabolic activation preparations. This report presents the results of the investigation. 66 Industrial BIO-TEST Luowbries, Jac. 2 1. Summary in sTehreietseostfmiatveirtiraol,miTc-r1o4b8i5a,l waasseayesxaumsiinnegdSflormomunteaglenaincd aScatciveihtayzomyces indicator oxganiarss. The test material was tested dixecty and inthe pre. cence of liver microsomal snayme prepssations om Aroclor-induced rate, bDootshethleevnelosmaocfei0v.a2t5i,on0.a5n,d 5, the aancdti5v0atuigonofesTt-s1.485Sopmere plate were used in physielogica effec Levels were below tose Loves. was observed at the highest dose level (50 ug/plate). The lower dose The results sbsined with the positive conteol materials demonstrate hat the tet systems are functional with moun matagens. The results of the tests conducted with T-1485, both in the absence and in the It presence of the was concluded rat that liver activation T-1485 did no system, were exhibit genetic all negative. activity in any of he 12 ire assays employed in this vestigation. Respect submited, INDUSTRIAL BI0-TEST LABORATORIES, BC. Report prepared by: St ein sHeteade Toscot Report approved by: =, 2~ ~ 2 ne Sinaier: Torkeiony som a 4/7 RE -- ---- The following strains of indicator microorganisms were used 5 2. Bacteria Strains: Salmonella typhimurium, strains TA-1538 TA-98 TA-100 The tissue homogenate and 9,000 x g cell fraction were prepared from the livers of adult male Sprague-Dawley rats. The animals were treated with 500 mg/kg of Aroclor 1254 five days before kill. `a sufficient sucrose and completely homogenized with a motor -driven homogenizing from thts preparation were weed dor the activation teste. 498 Jndustrial BIO TEST Loboralories, Inc. 4 G. Reaction Mixture testa: The following reaction mixture was employed in the activation Component I2R 1. vTTePeoNyoe (tsodnim eunma saalt) Sl hCDaeveirvalheonmto8gen2s5tmegtroacktiton D. Plate Test (overtsy Method Final Concentration/ml 2365H6 ipbpsmmoottmloeeensns strain weArpepradodxeidmattoelteyst10t9ubceesllcsonftraoimninaglo2g.0phmalseofcumlotlutreenoaf geaachsuipnpdliecmateonrted with biotin snd a trace of histidine, For nenactivation tests, the 4 dose Levels pofoutrheedteosvtermattheerisaulrfwaecrese oafddseedletcotitvhee acgoanrtepnltasteosf.theInaapcptriovpartiiaotnetetsutbsesthaend 5,000 3g tissue supernatant and required cofactors (reaction mixture) were added added to to the the overlay tubes. Four dose levels of appropriate tubes, which were then the test chemical were mixed and the contents poured over the surface of a minimal agar (selective medium) plate and allowed to snd scored for the solidify. The plates number of co were lonies i ncubated growing for 48 to 72 hours on each plate, Bos at 37 itive C, and solvent controls were run with each assay. 8 4/7 | Jmthsinial SVQ 1x31 Laborsionies, lnc. 5 E. Positive Control Chemicals Positive controls using both directly active positive chemicals and those that require metabolic activation were run with each assay. The following chemicals were used for positive controls in the nonactiva- tion and activation tests: Test Nonactivation Chemicalx Methylnitrosoguanidine 2-Nitrofl(uMoNrNenGe) (NF) Quinacrine mustard (QM) Solvent Water or Saline WDaimteetrhyolrsuSlalfionxeidests Probable Mutagenic Specificity BPsx FFosutr Activation 22--AAcnetthyrlaammiinneof(lAuNoTreHn)e Dimethylsulfoxidess* Dimethylsulfoxidess# BPS#k FSuk o 8-Aminoqu(iAnFol)ine (AMQ) Dimethylsulfoxidews* Dimethylnitrosamine Saline BFiSsH (DMNA) #4* CBoPnSce=ntBraastei-opnasirgisvuebnstiintuRteisounlts Section *#% PrFeSvi=ouFsrlaymesshhoiwfnt to be nonmutagenic 7 420 Lee Site ssi, ne. 6 IV. Results A summazy of the plate test results is presented in Table 1, The test material was evaluated at a series of dose levels such that the highest level (50 pg/plate) showed some physiological effect. The lower dose levels (0.25, 0.5, and 5 ug/plate) were below toxic levels. The results obtained with the positive control materials demonstrate that the test systems are functional with known mutagens. The results of the tests conducted with T-1485 were all negative. o 42/ Industrial BIO TEST Laboratories, Inc. i 3 "3roe- : 1 | 4 23s2ie agsvss || Pichs Hl] | Poonam |] : pERREE fERfe yar