Document GKyv3grzXJ70Jye2DvpyeNONN

WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC MONOGRAPHS ON THE EVALUATION OF THE CARCINOGENIC RISK OF CHEMICALS TO HUMANS Chemicals, Industrial Processes and Industries Associated with Cancer in Humans IARC Monographs, Volumes 1 to 29 SUPPLEMENT 4 Report of u IARC hoe Working Grasp which mot in Lrao, S>I2 February 1912 to adviee too Director, IARC. ao chewteth. iaduetrial pracomm tad iaduatriae that an earaiaogaaie for huaiaaa October 1982 INTERNATIONAL AGENCY FOR RESEARCH ON CANCER HONS 225114 METHOOt It Ttw data an each chemical war* .evtewad to data! batata aw meeton by aaMciaa mantaats at tha group- the tramat ctudtos and then-tarm taat raaifts ware ovtaueted by axpanmamalan and tajman tojdtM by m apppitMaglBL Ourtig tha wwatog at dw working group taa aaaaawnam* ware ftiat and adopted. and averse avtfuabora at cwctnoganpcy tor humans were mad* on tha baato at tha aomtanwd mwva tram humane and eapenmentat aytteme aabto 1). that daaptpbena at tha ddta an wtapi ta aaaaaamantt and evaluations wars baaad ara g*an at toe aadton an ftaetito. moanar mtn tetaranoas te tna Monograph vounaa to wrapt thay am tvatuttad pravtcupy and toan appeeatte. te papara pubaanad aupeequanay. Assassawnf at atrfpenca tor csreinafatocfty *am bdn at humane Endmoi of earonogsmorty from human rtudtot oemaa from taaa main aouroaa i. Casa tapona at individual eanear patanta who warn aapoaad te tha tfamnto or t*a*p!eunpos aptdamtotogtoai vtudtaa to wtapi toa toetdanaa at aarwar to rvnwi potatonon* waa found to vary to apaca or tana ntoh aapoaiaa to tna agwtts. 3. Analyse* aptdamtotogieai (can eararat and canon) ttudw at wrapt mditta ipoan id tha chamtcai or group at Pwntaais was kwto id be Mwcatw wtth vi nxMMd rtafc Of eanear Term cmene must ba mat before a cauaat aaaectotion ovt be tofarrad batwaan v There la no Mandied blaa wrapt oaPd aaptoto toe aaanrtabra. 2. The poaetadty of eonfbundtog haa bean eonatdvad and ntod out as arptwrang tha 9. Tha aatcPaicr la pPtoy to ba due to Pwnoe. at ganarto. atdtoupt a ato0a atody may >a WfciW P mum plaet tatatenpan. nipt ara aoncontam ai ahowtng toa aaeodedon. adtan to* aaaaatMon to atnjnJTwNto thann^a dadanaapendd^fitadonaWp. or atoan laduettan at nipaaiea a toda ad by a L ft Ilia If atodanpa P oarpnogantpiy. wrapt tnPcaaw that toara a cauaat taaaaratip betoiaan toa agent and marten canar. L Uaflpd wanes p carpnegarapty. wrapt topeanaa that a cauaP MMpmtMen a (P P HONS 225115 12 IARC MONOGRAPHS SUPPLEMENT 4 4eaeaamertf of *ld#ei tor arclnoftnictfy from alvdtoe to experiment#/ enjme/r That* aiaeaamenti daaaiflad nto tour group*: *. Sumernnt pmdance of earorogemcity. when indicates toot ffwrv ^ Mmim mctoanoa of malignant hpncuri: (t) to mirtpto apeoea or ttraan: or (b) In --Ap*. exoanmenta (preferably Mth different rout** of atoranietrabon or uair^ dMonnl doea tovaia); or let to an unusual degree Mth regard to nooanea, arts or lyps of uwr. or ago at onaat. Addltenal ovtoanoa may bo provtoao by data on rtnaa response oflaets. at w at information from anon torm taata or on chomcal atncture. a. Unrreo rnoanor of earanogoraoty. when maana that too data suggoot a rri>wr nc abaci out art limited because: (a) tha atudiaa nvoivt a angle apeeiee, atraai. or experiment. or (b) tha axpenment* art rattnctad by Inadaquata dosage tovato. hadaquata duration of axooaura to tha agont. naoaquata pmod of foaoeM*. poor aurvwai, too tow animal*, or nsdaquata raponng; or (e) tha neoplasm* groduoad oftan oeour agents- naouaiy and. m tha paat. have baan dtftaat to tfaaarfy as malignant by Nstotogcai ontona alone (e.g., katg and aver honours n mce). d. inadequate andonot. Mien vacates that because of major quastetive or quanwattva Hrrytattona, the studios cannot ba intarpratad aa thowmg atthar the praasnoe or toSince of a earonoganc eftoct; or that mom tha matt of the taata ueed. the cremcai is not earonoganc. Tha number of negative atudiaa ia amal, anoa. in general, ituow* that Show no effect are teas toaiy to be pubashad than Ooaa auggooting ctoOnoganuty m. No data indicate* mat data acre not avaitabi* to the Wonting Qroup. The catagohas auffctont mdence and armed evidonoe rotor only to the aoangth of the experimental andonoa that thaaa cfwmcafc art earonoganc and not to the extant of that uorcOtogenc activfty nor to tto macnantom tovotvad. The aaaadtoatcn of any STViwV nwy 9W91 n nvw vnonniwi osoDnwv vtmw> Baoauoa of the targe number and adds variety of ahorvam taata that may be relevant tor tha ptatPcbon of potential coronooana. to* data iifMva to each aompound have bean aurmamed at the torrn of tataaa Thaaa hdtoato both the typo of tool uead and tfw ntntegtrat oomptoxity of the taet ayatom OHA dtomppr ttefudaa aitdanea tor apnaiant butdng to OHA, ktdueoon of DHA braaaaga or repair, rcuceon of prophage at bddarta. and a poatova raaponaa at taata of oomparadva atrvtvaf at DMA npatoprodtotm and DHA raptoi rtodrtont bacaarto. >toa*gardaff' ratora to toduedon of ntotaaana at outoaad ooaa or in ongamama fa g- herttoBla aftorattona to phenotype. toeQjdtog forward or javam point muuttona, noombbtadcw. gana ooftoanfon. and tpadtobm muttdonl 'Cfratio aomil anowmar retort the todudton of deomoaomd abanattona. Idudng oraaka. gape, rawrangoman and mtorenuoat. datar ehromatH axtfwnga and an*toy. `Oder' retor* to vartowa addtoonai andpoetto. toetodtog aol tranafomadan (Tf, la., itcmhotogh eal banatonmden and ootony tormaaon at agar; damtoara latoar (DL) taata; merphatogi- eal MnemaMtoa to apantt ItA); and itwocftontotol rmaaaon (Mt). Tha btoto0oaf ayaama tooajda-. `tootaryctar. la., bactana. to tha ptaaanea or absence of an aeoganom mataboba aothration ayatam. and oduar ayatama; `Rimpr and ^een paafi ncctr, iiticdy Orooophaa iwaianogaaiar. Mammafan aade (to vtooy;jtthar raoant or twnan aomatto eaat or oal fetaa to gutum; 'Pfdmmdb (to aHof, atutoaa to ota* too toot eempeund waa adnantotorad to mtaet aapartnamal antmaia; and `Manana (to vtvoy. atutfaa of oaaa bom groups of Wduda draam bom a poptiabon anpoaad to tie uboanea m auaaben. HONS 225116 METHOOS 13 in MU tau, mdfcatu mat ma maun *u judgid by H wvu* Qnxs m u tigniPeantly poamva rt cno or mom ituyi; v ndtoatu mat wu frdgad to W iwim from an avahiabon of ona or mom auiyi: and T todtoatot M eontradetorv mart* wat oMfrnad n uaaya from ddfarant laboratonu or n dMaram y tvatarm or mat tha mcun *u judgad to ba aqutvoeai. Tha mdlvidual tabtoe tar mu oontooimd'ara tummantad, tor purpoau of eompartaon. n Apeandli 3. Tha ovarai avtoanoa tummantad in mt tabto u adludgad to lai two ona or rvaa eatogonu. M^ewnt. arrated and nadagutra: i Suttaam awoanoa. whan mar* warn at tout mm* poamva mautta m at taut two ot thru toot ayatama maaaimng DMA damagt. mutagampty or ehmmoaumai attoeta. Wlwn two ot tha poamva ntttti wara tor ma aama gtnaot aftaci. may had to 6a danvad from ayatama ot diftarant 6<otog oomptoxity. i, Lmtad avtodnoa. whan mam worn at laast two posit** mautta. adhar tor orffarant andootnta or in ayatama memaanting two tawata ot btotogieai eomptaxfty. i maddduat* awpdnu. whan mam w*m ganaraay nagathm or only ona poamv* tut raautta. uo to two poamv* tut mauts w*m oonaidamd inadaquat* a th*y r accomparvad fry two or mom nogativ* tut mautta. Tha Wottong Group wu unaota to dahna entarta tor nagattv*' avidane*. In utaMatong m*u eatogonu tha wonting Group gov* gmator watght to tha ttou primary andpomta ONA damaga. mutaganicity and eiaianwaomat attoeta . and ludgamant* worn mad* on tha quality at w*i at on m* quantity at m* avtdanoa. m a minority ot caau. atnet mtammtatton ot mau ermna wu tompwad Oy oonatoaraaon of a vwiaty of othar taetom (autfi u ma putty at ma taat oompouw. proOtoma of matuokc activation, approonatanau of tha taat ayatam) wfven. m ma ludgamant of ma working Group, would plaoa opmgound <n a eatogoty adeva or batow that mpeatod fry tha aummary taOto. fraMtoi afaamtnapantt ttofr to human# At pmaant. no oOfrcm* oitorta aitot to marpmt data from ftodaa at aiparknantai ananato or from ahon-torm toata mrnedy m tonna ot tunan Ml Thta. m *w ahaanw of autllatont avtdtowa from hunan aiudtoa. avaluatton ot ma oarchwganto ttok ip Humana w*a aaaad an oonaidraaen at bodi m* aptoamietogtoai and anpartmamai tnoanu. Tha uiaitoi of m* eatogonu of tnoanu dahnad aoov* a*ow* aubatandai vartaaon wtmm ueh. Tha daototorw maenad Oy tha fro* mgartong ovarat ttok noorporatod mau dMarsneu. avan mou^t may ooua not atomy* o* mhactod adaguawty m ma ptooamant of an aapoaum mto a partcutor estogory. u totod m TaOto t, Tha chamieali. poupa at ctwmicaN. mduaotal mouiiat or oncaagnai anpoauma wm ax* put no ona of mm* group*: HONS 225117 14 MAC MONOGRAPHS SUPPLEMENT 4 Grot*? tfmeif, gfnf MmcH. MMfiif prami or ooemtiano/ uumm * pvett&r owync hariana. tmo eatogory mctudot imewn tor wh*n, at on* art*mo. (ho awdano* of lunan coronagorwty atmoai ouMaonr, m w*a M oipoai#** tor whoh, at (ho othor oitomo. 4 nadoauct* To noAoet (ho rongo. (ho eow^o'Y ** dtadoo otto hghor (Gnxo 4) and kmw |(Vno *) dtgroot ol ntlmt uawaay. aotogwy 24 h noorvod tor axpoourac (dr when (horo woo ot loool Pravod ndwi of earanegoncrty to hunona. Tho data from otudtoo In oxponmontai anmdB ptoyoo w< important ret* n Manning atudtn to cotogory 2. and pamouwiy trooa (n Group B, mm. m* oompmodon of auffloant andanco in aroman and nodoquota data In remrena uout*y roartad ri * ooaarfcaaon of 2B. tn aomo caaoo. tno Working Group oonoioorod (hot (h* Known chomcat preportio* of compound and (ho rooUia tram tnort-torm toata alowod a* tranator (ram Group 3 to 2B or from Group 21 to 24. Gnxp J Tha ohontdaf. 7*ixp of ehormcad, rttamat preeaaa or opctpolonar Mponrt earner 0* otaaaiflad a* to da oaronogoracKy to fnariano. RESULTS AND CONCLUSIONS Tn* ataoaamanta of dagroo* of ovidanoo tor carctnogonfcrty to runout and n oiponmontal animoto and tor actMty m ahon-lorm tooth al tho aummary atamodon* of eorcinogonte rtoK to hmwt* or* gwon at TaBt* t. Grou> r: Tho Wonting Graf condudod mot (ho toOdnlng 7 (nduemol prrwooaaa and oocupodonat wowaoa and a cnorhcatt and group* of damtaata aro eouooty Boot and aho* manufacuo and repair HONS 225118 RESULTS AND CONCLUSIONS Qwnicala and 7093 of tfiamical*: *-Arrwab&wvfl Anwgaalr mufcnaa oofttanng phanaoatn* atmtk and imnc oompomda* Aaeaaioa AiaBaoprma Samcne M.AABaff<NOfty>*tapt*y<amna (OtfomapAattoa) v^0WQnwnyi|iw w aonracp^ioi 9wiwif fnvviyi fviir 1 4-tuunatfoi omamanaauipfwnata (Mytaran) Cartan oorndnad cnamotharapy tor tyiwphomaa1 (Inducing MOP^) gaprembucl Cwton and caftan dwan oorapoinda* Coryugatad oaatrogana* Cyttopfloapnamda Oatnytcaaw# Maddtnan Maffwiialan tm ifta-vtolat A narapy (PUVA) Muatardgaa 2-Napwttytawna Soota. tara and a" TraoauVwn Vtnyl Mcrtda 15 Onup t. Tha todcwng di tfawacan. gratia of dtowacaN or Muaffal preeaaaaa ara piracy caranoganic to laanana QmmiA aryftmand Otadtid anprwa Otmadtp cu^ftH ar*Ta NONS 225119 IS IARC MONOGRAPHS SUPPLEMENT 4 0nu02B Acdnomygn 0 Adnamyan Arnirat Auramno (ta<*in(e*i grad*) SiozotncNoadi lacnwroamyi mteiouw (*C*U) Caen*** and oMm oomeomta Carton tatracftionda CMaramphonooi 1 ^OaorotyiytyVcycionary*-1 -nrtroaouraa (CCNU) CMorgtotm Chloratnonota (decupatonaf aapeowa to)* Oaptaan DaeartaiMo DOT j.j -oapooonina Dianoaatrai 3.3 -OanothoKytanwma lordicvttanwann) Dtmatnytcartamoyi taojnda 1.4-Otoaana Oiract Mat* 31 (tactmcaigrada) Uraet Skra ftacMeai grade) Bract Brown M (tacnwrai grada) EptoNoroftyam EmnytoaotadU H)*ua OattaoaMTI tonypiw *r * TadacMafo^rm |di foam (TCOO) 14JiTWderagMnai TrNCaMMPgddia-tantBdt*na(Tdaaquc>iM THRl^NMktyQpfwgnna augPWa (TNotapa) (Pate ft Tta W I not to rtehtenana. and HONS 225120 RESULTS AMO CONCLUSIONS 17 Tabto I. Lnwy avatoatona of caror>ogarc n*k to toanana front ohamtoila, Muotrtoi proeNMi and vtduairtoa' baaad on avtdanoa lor oaroatogantoty to luwo artmata and tor aetMty tt anort-tarm taataT Chamaal, proeaai or Mutoy toyowwi AcTtnemyon 0 Atftamyon Aftttoaata todrtn 4-Ananotoprtanyt Artnmo Anaaafftanca. rototao AntiQatic rntibm oontaMng pNMOIfln totonaeaan A/tona Ananc and oortam araanc oompom* AIMOt Atnmata (lacfvtfcal grada) Wanutacuv of auramna Autwaia ftanrfu ItnoM* - (torn tor earo- IMM fradaduato fradaouato totd^uatt aufflctont fcadaqutta tnadaduata aufMar* Imnad inodaduato auMefani tuflMnt mnad uMtnt ftAM tufftcJvnt auMefani Cvtdsnoa tor ears- auMgm MH0 auMdant awlMani Imnad awiWom unpum nadaguata Imnad auMetom InvM nadaduata awlMani Imnad * brMid IMUfl nMvi Ivtoanea tor aetMty tt toata aufltoton aufftcfcftt awlMani HIM rtadaduata awlMant irMdnuftit NdiQuitt no data Ktod tnaoiQuatv IfflNtd rtadaduata MMant mum IMUfl iMnt Svanmary avaiuMert of oaronagame naa totoanana 2A 2d 2d 2A 3 1 2d 3 1 2A 3 1 1 2d 1 1 1 1 iMfiMtoiai itmtMC* 1 MONS 225121 II Ciwncat, i or nduatry (ARC MONOGRAPHS SUPPLEMENT 4 tor Mwy vaMflon gfcvttnortak HaoBiydna 1.4-putanadtt danathanaaJphawata (Mytaran) Cadmaan and cadman Caitoni Cartan oomtanad (tnduOng MOP*) CNoranttud CftAQfwnpfaoniool CNontantfHtptartor i An ua>i|fl)-9-cy0oftaxyt- 1 nttoaouraa (CCNU) (produrton of): CNoroohano* (< aapoajaaiB) CMorapnna Qnman and oartaln tfawAan oonpcnaida I 1 M aoNoart inadaquata MM auMOam 1 3 <Cr Vt) (CrW) 3 3 3 M 21 2* 3 1 It 3 3 3 1 DOT ortho owaorddaniana 3 2* 3 2t 3 RONS 225122 RESULTS AND CONCLUSIONS IS Chamcaf. proem* or industry 3.3`-O0orooanadins Otaunn OWiifi aulprtato j,3^mawyoaraj(*na |ornv Diantartlna) UVWI VWM Dimatnyi sutpnata 1.4-Otoaana IhtW OPwnI imytmaouda fVtytana taouma LAanwidi Fomaidanyda (gaa) HaucNoracyddftaaana KyOatoana Hydraans Bool ana ahoa "anuTaeaaa and rapair foartdn ococaaons) Carpanvy and (canary (oartdn FundknmanuNeWd Laatfar goods mamdPcWt Laatar tamnp Uattar and aawmidduaPy and papar mararfacMa ncganwty hiwnana ttymoty ftdanea or ooMly tfWMomi Mott Summary mMtot gfearaawgsNertak omanano nunutu nadaqua* InNONQuiit amnad -^-rrT frwdaouatt macMquaM maatuaa madaquaa madaquaa maaquaa iMquan madaquaa IMquili tnadaquata Mdaquaii tadawa MAoant WdsquNiN knM auMoant aurtdom auMoant aurtdam auMdam auMant aurtdam inttsd auMdant uMam amrtao irmw umm aufltaM mnod uAm mnad aufioam auMeara ir^aaouata auNgam autaant auMdam ImMsd ImMsd sufRdw MdaquM suMcitAt sufRdtm 2* 3 3 1A M M 2A M 2* 2* 2* 3 2* 2 3 auMdam * * 1 m2 auMdam . a 1 hadapuata * - 2 madaquaaa - 2 nadaquata - * 2 2 Land and I 1 ) 1A 2 i s HONS 225123 20 lAflC MONOGRAPHS SUPPLEMENT 4 Mathotraaata Matnoiaaten with uttravmat A marapy (Auva) Matronoaxote Muatard gaa I.Naphthytamna 2-NapMhyiamna mcaai fimnj nkmi arte oanam nckai oompowtea Nitregan muatard |$a atee Cartate eofftenad ___ ohamotharapy ter lymphomaa) Oaatregana arte progaatlna Conpinad oral oontraoapttvaa Saquarteal oral oontraoapOvaa Othar oaatrogan-progaatn eormnattena Conjugated oadteogana Evteanoa ter oarte. nOQtntfty n tormn (dOra ter cant jagantety nadaquate untetont nadaquate udicnnt nadaquata vffltolont nadaquata Evtoanoo tor oetMfy to Itert-tann testa Stannary valuation tav ganeflan ID toman* RONS 225124 RESULTS AND CONCLUSIONS 21 HONS 225125 ili 22 IARC MONOGRAPHS SUPPLEMENT 4 ChartiicaJ. OroocM or Maty iMm lor caret' mgancNy mrwnana or oartt fianm* Evttanoa ar ocaotiy Wlgm Summary Trta(aidiny<>*arantoquona ougntdo fThmtapa) Underground haamaOta mating (with aapoaura to radon) Hooman* Uractf muatard vmomana vmortatma (Saa nae Cartam ooivttMd tfwwtfwtpy flw lyinphunw) VTny(onda V0)Min9 (Morttfl madaquata madaquata auMetanl madaquata MdtQUfli madaquata MNad MM madaquata MfflQMAt madaquata MM * madaquata auMotam ****** i 3 2* 3 tnadaquvt* mMeHM naomrrT MdaquM imftod hidiqurtt miMiik ***** 3 1 3 MOMS 225126