IA M)(xRAHS ON TH EVATION OF TH CACINOGIC RISK OF CHICA 'I MA: Sorn Fugants, the Herbicides 2, 4-D and 2,4, 5-T , Chlorinted Dibnzodioxins and r1îscellaneous Industrial Chemcals Volur 15 Ths publication represents the views of an IA i'hrking Group on the Evaluation of the Cacinogenic Risk of Chemcals to M: which rnt in Lyon, 8- 15 Febru 1977 1977 IA IDRK GR ON TH EVTION OF 'I CAnnC RISR OF OICA TO MA: se FUGA, 'l HEICIDES 2, 4-D AN 2,4, 5-T, ClRITE DIBEODIOXIN AN MISCS INUSTR OICA Lyon, 8-15 Februar 1977 Mes 1 Dr A. Abbondolo, Laratorio di Mutagenesi e Differenziarto - C.N.R., Via Cisanello 147/B, 56100 Pisa, Italy Dr F. Berrino, Istituto Naionale pe 10 Stuio e la Cua de 'lri, Servizio di Epidemologia, via Venezian l, 20133 Milan, Italy Professor E. Bolan, IDndon Schl of Hygiene an Tropical Maicine, Reppel Street, IDndon W:lE 7Hl, UR (ChiY'an) Dr I. Cherozanky, Insti tute of Onolog, Maical Acem, Sofia 1156, Bulgaria Dr L. Fishbin, Assistat ta the Director for Enirortal Surillace, National Cente for Toicological Reeach, Jefferson, Arkas 72079, USA Dr R. Gingell, Assistat Professor, Th Etley Intitute for Rech in Cacer, Uni versi ty of Neraska MEical Cete, 42nd and De Aveue, Cì, Neraska 68105, USA Dr H.C. Grice, Director, Bueau of Chcal Safety, Health an Welfare Cada, Heal th Protetion Branch, 'Iey 's Pasture, ottawa, Ontaio RlA OU, Cada Dr J.E. Hufe, Director, Biciical Science Setion, Inoi:tion Ceter Calex, Infoi:tion Division, Oa Rige Nationl Laratory, PO Box X, Oa Ridge, Teessee 37830, US Dr P. F. Infante, Indutr-Wide Stuies Branch, Division of Sweillance, Hazard Evaluation an Field Stuies, National Institute for Occupationl Safety an Health, Ro A. Tat Laratories, 4676 Columia Parkwy, Cincinti, ohio 45226, USA lUnale to atte: Dr B. Paccagnella, Università di Padava, 110 Istituto di Igiene, Policlinico Borgo Ra, 37100 Verona, Itay 2Preset address: Unit of dica Cacinogenesis, Intertiona Agency for Resech on Cace, 150 Cours Al Ths, 69372 Lyon Céex 2, France 3 Professor D. Neub, Institut für Toxiologie und Ehryonal-Phaologie der Freien Universität Berlin, G3strasse 1-9,1000 Belin 33, FRG Professor G. Prodi, Director, Isti tuto di Cacerologia, uni versi tà deg li Studi di Bolog, Via S. Giaco 14, 40138 Bolog, Italy Dr G. Saint-Ruf, C.N.R.S., Cetre Macel Delépine, Service Saint-Ruf, Dépaemt de Chime Organique-Biologique, 45045 Orléans Cedex, France Professor C. Schlatter, Directar, Inti tut für Toxiologie der Eidgenössischen Technischen Hochschule und der Universität zürich, Schorenstrasse 16, CH-8603 Schwerzench bei zürich, Switzerland Dr V. F. Sirrm:m, Mager, Microbial Geetics, Stanford Reeach Insti tute, Melo Park, California 94025, USA Dr B. Teichm, Akdeme der Wissenschaften der DDR, Zentralinsti tut für Krebsforschung, Lidenrger Weg 80, 1115 Berlin-Buch, DDR Dr V. S . Tuav, Cacer Research Ceter, USSR Aædem of M:cal Sciences, Kashirskoye Shosse 6, M'SCC1 115478, USSR (Vice-ChaiY'an) Professor V. Vojvodic, Buevar Revolucije 257/III, 11000 Belgrade, Yugoslavia Observers 1 Dr O.H. Johnson, Seior Industrial EcnoTIst, Chemcal-Environrtal Progam, Chemcal Industries Ceter, Staford Reseach Insti tute, Melo Park, California 94025, USA (Rapporteur sections 2.1 and 2.2) Mrs M.-T. van der Vene, Cassion of the Euope Ccities, Health and Safety Directarate, Bâtirt Jea M:mnet, Avenue Alcide-de-Gasperi, Kirchbrg/Luxemurg, Great Duchy of Luxemurg Dr S. Villa-Trevino, Professor and Chim, Cetro de Investigacion y de Estudios Avanzados del Intituto Politecnico Nacional, Depart of Cellular Biolog, Apdo Postal 14-740, rlxico 14, D. F ., Meico lUnable ta attend: Dr L. Rizem, r: Chemcal Euope S.A., 8810 Horgen, Switzerland¡ Dr E.E. Tutle, Pesticides Spcialist, Plant Protection Service, Plant Prouction and Protection Division, Foo an Agriculture Organization of the United Nations, Via delle Term di Caacalla, 00100 Ro, Italy 4 Representative frcr the National Cacer Inti tute Dr S. Siegel, Cordinator, Tehnical Infoi:tion Acivities, Ro C-216, LaC1 Building, Bioassay and Cacinogenesis Progam, Divisibn of Cacer Cause and Prevention, National Cacer Inti tute, Bethesda, Malan 20014, USA Secretaiat Dr C. Agthe, Chef, Foo Adi ti ves Unt, i"IO, (":ieva Dr H. Basch, Unit of Chcal Cacinogenesis (Rapporteur section 3.2) Dr L. Griciute, Chef, Unit of Environrtal Cacinogen Mrs D. ~lietton, Unit of dical Cacinogenesis (Library assistant). Dr R. Montesano, Unit of Chcal Cacinogenesis (Rapporteur section 3.1) Mrs C. Parsky, Unt of Chemcal Cacinogenesis (Technicai editor) Mrs 1. Peterschntt, Unit of Chemcal Cacinogenesis, i"IO, C':ieva (Bibiiographic researcher) Dr V. Ponomkov, Unit of Chcal Cacinogenesis Dr R. Saracci, Unit of Epidemolog and Biostatistics (Rapporteur section 3.3) Dr L. Tbtis, Chef, Unit of Chencal Cacinogenesis (Head of the Programe and Secretary) Dr H. Vandekar, Meical Officer/Toxicologist, Division of Vector Biolog and Control, WHO, Geeva Mr E.A. Walker, Unit of Environrtal Cacinogens (Rapporteur sections 1 and 2.3) Mrs E. Ward, Montignac, France (Editor) Mr J .D. Wilbur, Unit of Chcal Cacinogenesis (Co-secretary) 5 No te th reaer Every effort is made to present the nnnoaphs as accately as possible wi thout undul y delaying their publication. Neverteless, nustaes have occured and are still liely ta occu. In th interest of all users of these nnnographs, readers ar reqste ta coicate any errors observed to the Unt of Chcal Cacinogenesis of the Interntional Agency for Reearch on Cacer, Lyon, France, in order tht these can be included in corrigenda whch will appe in suseqt volurs. Since the nnnogaphs are not inteded te be a review of the li terature an contain onl y data considered relevat by the WJrkig C':iup, it is not possible for the reader ta detenne whether a cert stud wa considered or not. H~ver, research ~rkers wh are awe of imrtant published data tht rny chge th evaluation are reqted ta mae them available to the abve-metioned address, in order tht they ca be considered for a possible re-evaluation by a future WJrki f':iup. 7 cn BA AN PUE OF TH IA ~ CN TH E.TION OF TH CAINC RISK OF OICA TO MA .............. 11 SCPE OF TH M) 11 ME~ FO PRCIN TH M:HS 12 GE PRJIPLE FOR TH EVION 13 EXLATORY NO ON TH M)HS 16 GE RE ON TH St COSIDER 27 TH M)HS l, 2-Bis (choraæthoxy) ethe 31 1,4-Bis (choraætloxythyl) l:ene 37 Chlorinte dizodoxi . .... ............... ............ ... 41 Coper 8-hydrxyoline ... ........ .... ...... ......... ...... 103 2, 4-D an esters ............. ... ..... .............. ..... ..... 111 l, 2-Dibrar 3-choropropae .......... .................. 139 trans- l, 4-DichorObute ........ ... ...... .......... .... 149 DihydroxyzenesCatel .......................................... .. 155 HydroneResorcinol Dimthoxae .............................. 177 Eosin an eosin disodum salt .. ........ .... ..... ............. 183 E'tleIe d.rade ........................................... 195 Hexthy Iphosphoramde ...................................... 211 Isoprol alcohol and isopropl oils ......... ............ .... 223 Methyl iodde ... ......... .............. ................... ... 245 ~ra-Qne ................................................. 255 Succinc anydride ......................................... .. 265 2,4,5-T an esters ......................................,..... 273 l, 2, 3-Tris (chloraæthxy) propae ... .... .............. ........ 301 APPENIX A ...... ...... .......... .... ... ..... ... ... ................ 307 SUPLE CORRGE TO VOll 1-14 .............. ......... ... 341 CU INEX TO lDNHS ............ .......... .......... .... 343 9 Bl AN PU OF TH IA PR CN TH E.ION OF TH CA:IC RISK OF CHCA TO MA The Interntional Agency for Rech on Cacer (IA) intiated in 1971 a progar te evaluate the cacinogenc risk of chencas to ll. Ths progar wa support by a Reolution of th C':ierg Cocil at its Ninth Session concering the role of IA in praviding governt authorities with exrt, indepedent scientific opinon on environrtal cacinogenesis. In view of th i.rtce of the project an in order ta exite prouction of irnogaph, the National Cace Intitute of the Unted States has pravided IA with aditional fun for this purse. The objecive of the proar is ta elabrate and publish in the fonn of irnogaphs critical review of cacinogencity and related data in the light of th present state of knC1ledge, with the fina aim of evaluating the data in te of possible h1J risk, and at the sam tim to indicate where additional research effort are neeed. SCOPE OF TH M:HS The rrnogaphs s'lize the evidence for the cacinogenci ty of indi vidual chemcals and other relevant inoi:tion on the basis of data coiled, review an evaluate by a WJrkig Group of exrts. No recan medations are given concerg preventive rnasures or legislation, since these matters deped on risk-beefit evaluation, whch se best mae by individual governts and/or intertional agencies such as WHO and ILO. Since 1971, when the progar stad, four previous volurs have be publishe! -1 4. As new data on checals for whch rrnogaphs have already be prepaed and new principles for evaluation bear available, re-evaluations will be made at future metings, and revised rrographs will be published as necessary. The rrnoaphs are distribute ta intetional and governntal agencies, are available te industries and scientists deling wi th these checals an are offered ta any inteeste reader thugh their world-wde 11 distribution as WHO publications. Thy also fonn the basis of advice fror IA on carcinogenesis fror these substaces. MEISM FOR PRODUCING TH IDNOHS As a f irst step, a list of chemcals for possible consideration by the Working Group is estalished. IA then collects peinent references regarding physico-chemcal chaacteristics*, production and use * , occurrence and anlysis* and biological data** on the se caunds. The rrterial on biological aspets is sllized by an exrt consultant or an IA staff irr, who prepaes the first draft, whch in sa caes is sent to another exrt for ccnts. Th drafts are circuated to all irrs of the Working Group abut one rrnth before the meting. Duing the rrting, further additions to and deletions fro the data are agree upn, and a finl version of cots and evaluation on each cound is adopted.