Document ByLBBOByVr4ev1zb0gepXjVz4

L Tomafis ef af Humans T.i/'lr 2 Confirm'd Animals Chemical or indus- Main type of ex- trial process posure" Target organ 13 Cyelophospha- Medicinal mide Bladder i \ Main route of exposure* p o . mjection Animal Mouse Rat Tnrgpt organ Route ol cxpo'.im Hemopoietic system. lung Various sites Bladder* Mammary gland Various sites ip sc miechor Po *P 'P 1V 14 Oiethylstilbes- Medicinal trol Uterus, vagina po Mouse Mouse Rat Hamster Squirrel monkey Mammary Mammary, lymphore- ticular testis vagina Mammary, hypophy- sis' bladder Kidney Uterine serosa P 0. s c injection s implantation Local s c implantation S C injection, s r implantation s c imo'afitation IS. Hematite min- .Occupational Lung mg (? radon) Inhalation Mouse, hamster. Negative guinea pig Rat Negative Inhalation 11 s c injection 16 Isopropyl oils ^Occupational* Nasal cavity, lar- Inhalation ynx 17 Melphalan Medicinal Hemopoietic sys- p o . mjec- Mouse lem lion Rat 18 Mustard gas .Occupational' Lung, larynx Inhalation Mouse No adequate tests Initiator 1 Lung, lymphosareo- mas Local Skin 'P 'P Lung Local mammary inhalation i s c miecl'on 19. 2-Naphthylam- ^.Occupational* Bladder fne Inhalation, skin, p o. Hamster, monkey Mouse Rat. rabbit dog. Bladder Liver, lung Inadequate p0 s c inieclion p0 20 Nickel (nickel ^Occupational Nasal cavity, lung Inhalation retining) 21 N,W-Bis(2chloroethyl)2-naphthy- lamme Medicinal 22 Oxymetholone Medicinal Bladder Liver p0 po Rat Mouse, rat ster Mouse, rat ham- Lung Local Local Mouse Rat Lung Local No adequate tests Inhalation sc .in injeeho i m implantalior iP s c injection 23 Phenacelm Medicinal Kidney Po No adeq.uale tests1' 24 Phenytom Medicinal Lymphoreticular p o , injec- Mouse tissues tion Lymphoreticular tis- P-O.. i p. sues 25 Soot, tars, and iJOccupa* oils Jjonatr. environmen- tal Lung, skin (scroturn) Inhalation, skin Mouse rabbi! Skin Topical 26 Vinyl ehlonde ."Octfupatfonat* Liver. brain/ Inhalation, tungr skin Mouse, rat Lung liver, blood Inhalation vessels mammary, Zymbat gland, kidney " The main types of exposures mentioned are those by which the association has been demonstrated, exposures olher than tho mentioned may also occur * The mam routes of exposure given may not be the only ones by which such effects could occur r Indicative evidence * The induction of tumors of the nasal cavities in rats given phenacehn has been reported recently (S Odashima, person communication, 1977) 9051572880 CANCER RESEARCH VOL RSV0033793 u wv wi l^ii w vv w v/ y v* * vi t f v vrnumiUUiO nary tumors in rats The causative agent in hematite mining was found and those lor which the data were judged has not been identified, and the role ol radon is suspected inadequate forevaluation Ferric oxide was'not carcinogenic in mice, guinea pigs, or Of the 368 chemicals evaluated in Volumes i to 16 of the hamsters'when given by inhalation or mtratracheally. monographs, the 26 associated with carreer induction in Correlations between human and animal data should be humans have been referred to previously For 221 of the somewhat easier for the remaining 21 compounds, because remaining 342 (Table 3), some evidence of carcinogenicity in most of these cases a single identified chemical is in 1 or more animat species was found. It should be stressed involved. One notable exception, however, is arsenic com that for these chemicals (marked with an asterisk) no pounds Occupational exposure or exposure of the general attempt was made to distinguish between those for which population to drinking water containing high levels of "strong evidence' and "weak evidence of carcinogenicity, arsenic or to arsemc-containing drugs is associated with following the criteria discussed m the last part of this paper, the occurrence of skin cancer, while lung cancer is also existed or those for which additional confirmatory carcino associated with occupational exposure. No definite carci genicity studies are needed For the majority of these nogenic effect has been observed in the available results chemicals, evidence of human exposure exists but no from expenmental studies. evaluation of the carcinogenic risk to humans was made, For 5 of the remaining 20 compounds, namely, benzene, either because no epidemiological studies or case reports chloramphenicol, isopropyl oil, oxymetholone, and phena- were available (205 compounds) or because the results cetin, no adequate carcinogenicity tests were available for were inconclusive. (Some case reports were available for 7 evaluation at the time that the monographs were prepared compounds. BHC/lmdane. carbon tetrachloride, chloram However, recent unpublished results indicate that phena- bucil, dimethyl sulfate, iron dextran, tris(aziridinyl)-p-ben- cetin is carcinogenic in rats (S. Odashtma, personal com zoquinone and tris(1-aziridinyl)phosphine sulfide. Results munication, 1977). The other 15 compounds were carcino of sorrte epidemiological studies were available for 9 genic in at feast one, but mostly in more than one, animal compounds, amitrole. beryllium compounds, DDT. dieldnn. species. dimethylcarbamoy! chloride, isoniazid. lead salts, pheno- Comparison between target organs in humans and ani barbital, N-phenyl-2-naphthylamme.) mats confirms that the carcinogens have, in some cases, the For the remaining 121 chemicals, the available studies same organ specificity in humans as that in experimental were inadequate to make an evaluation of the presence or animats In most cases, the chemicals were tested in more absence of a carcinogenic effect in animals or humans. than one animal species, but the similarity in organ specific ity may be limited to only one of the animal species tested The chances forstmtlar target organs are apparently greater f similar routes of exposure are used (Table 2). However, Conclusions and Discussion For 26 chemicals (or industrial processes) ol the 368 chemicals that were found to be carcinogenic in both evaluated in the first 16 volumes of the IARC monographs, humans and animals were carcinogenic in the latter also an evaluation was made ot the positive association between when administered by routes different from the one by exposure and occurrence of cancer in humans (Table 2) In which humans are exposed The target organs in animals these cases, the presence or absence of evidence o,a carci are more often multiple than in humans. nogenicity in test animals was not used in the formulation The evaluation of the carcinogenic risk to humans of of the evaluations as is shown, for instance, for benzene these 26 chemicals or processes was based on evidence and arsenic compounds One important lesson from these provided by epidemiological studies or case reports, and human carcinogens >s that experimental evidence has in experimental evidence of carcinogenicity was not used m some cases preceded human evidence, and a similar effect the formulation of the evaluation For several chemicals in humans might have been predicted. (aflatoxin, 4-aminobiphenyl, bis(chloromethyl) ether,dieth- For 221 of the 368 chemicals evaluated in the 16 mono ylstilbestrol, melphalan, mustard gas. and vinyl chloride), graph volumes, some evidence of carcinogenicity was experimental evidence of carcinogenicity preceded human found in at least 1 experimental animal species (Table 3) evidence and a similar effect in humans could have been Humans are or can be exposed to the majority of these predicted The case of bis(chloromethyl) ether is slightly chemicals In some instances, results of epidemiological different from the others The first observations in humans, studies or case reports were available but provided insuffi indicating an unusual clustering of lung cancer in occupa cient evidence on which to base an evaluation In most tionally exposed workers, were made as early as 1962 (45, instances, however, epidemiological studies or case reports 46) Evidence ol a carcinogenic tffect in animals was first were nol available (the general scarcity ol epidemiological published in 1968 and preceded the publication ol the hrst studies noted throughout the monograph jnogram must be 2 epidemiological studies, which appeared in 1973 (25) stressed) In no case was an attempt made to interpret Chemicals Carclnogenicto Experimental Animals. While animal data directly in terms ol human risk or in terms of in 196B it was considered that fists of carcinogens should the degree ol carcinogenicity evidence provided by the not be prepared without an m-depth evaluation of the expenmental data However, a large number ol food addi available evidence, which differs both quantitatively and tives. pesticides, and herbicides have been reviewed tor qualitatively from compound to compound, an attempt is their toxicity by national and international agencies, and for now made to separate chemicals evaluated tn the first 16 a number of them the experimental evidence of carcino volumes of the IARC monographs into those for which genicity was considered sufficient to issue specific regula some evidence of carcinogenicity in experimental animals tions or recommendations (39. 47) Therefore, insofar as april 197b 90S1573 881 i \ f I ii; i i >r { \ RSV0033794 L. Toma/is el at Table 3 List of chemica/s lor which there ts some evidence of carcmojemcify m experimental animals only or for which the oata were inadequate lor evaluation oI the presence or absence of carcinogenicity (IARC monographs. Volumes I to 16 For (ho 26 compounds evaluated as carcinogenic to hitmans, see Table 2 1 Acetamide'" 49 y-Butyrolaclone 2. Acridine orange 50 Cadmium acetate 3. Acrillavlnium chlo 51 Cadmium chloride* tolgene" 97 2,5`Diarmriotoluene (suitate) 138 Disultirum 139 Dithranol" 140 Dulcm. 189 Lead caibonjH; 190 Lead chromate 19t lead phosphate' ride 52. Cadmium powder* 98 Diazepam 141 Endrtn 192 Lead subacelale' 4. Actinomyctns* 53. Cadmium sullate' 99 Diazomethane' 142 Eosin (disodium 193. Ledate 5. Adnamycm 54 Cadmium sulfide' tOO Dibenz(a,ft)acri- salt) 194 Light green SF' 6 Aidrin 55. Calcium arsenate dine* 143 Epichloro hydrin* 195 Lindane* 7. Amaranth 56 Calcium chromate* 101 D.benzfa./jacridine' 144 t-Epoxyethy|.3.4- 196 Luteoskyrin' 8. 5-Aminoaf**- 57 Canthandin* 102 Dibenz(a.h (anthra epoxycyclo hex 197 Magenta* naphthene 58 Carbaryl cene* ane' 198 Maleic hydrazide' 9. p-Ammoazoben- 59 Carbon tetrachlo 103 Dibenzo(c,g}carba- 145 3.4-Epoxy-6-melh- 199. Maneb zene* ride* zole' ylcyclohexylme- 200 Mannomustine (c 10 o-Aminoazotoluene' 60. Carmoisine 61 Catechol 104 Dtbenzo(/i.rst)penU aphsne* thyl-3,4-epoxy-6- hydrochloridel' methyl carboxyl- 201 Medphatan 11 p-Aminobenzotc 62 Chlorambucil' 105 Dibenzo(a,e)pyrene* ale' 202 Medroxyprogestei acid 63 Chlorinated diben- 106. Dibenzo(a,/) 146 cfs-9.10-Epoxy- one acetate' 12. 2-Amino-5-(5-nitro- zodioxins pyrene* slearic acid 203 Merphalan-f 2-turyl)-1t3,4* 64 Chlormadinone 107 Dibenzo(a.i)pyrene* 147 Estradiol mustard* 204. Mestranot' thiadiazote" acetate' 108 Dibenzo(a,/)pyrene` 148 Ethinylestradiol* 205 Methoxychlor 13. 4-Amino-2-mlro- 65 Chlorobenzilate* 109 1,2-Dibromo-3- 149 Ethionamide' 206 2-Methytaziridine phenol 66. Chloroform chloropropane* 150 Ethylene dibrom- 207 Melhylazoxymett 14. Amttrole' 67. Chloropropham 110. Dibutylmtrosamine' ide' nol acetate' 15. Anitine 68. Chloroquine 111. o-Dichtorobenzene 151 Ethylene oxide 208 Methyl carbamate 16 Anthramlic acid 69 p-Chloro-o-tolui- 112. p-Oichlorobenze 152 Ethylene sulfide' 209 N-Methyt-AM-dm. 17. Apholate dine (hydrochlo 113 3,3'-Dichlorobenzi- 153 Ethytenethiourea' trosoaniline' 18. Aramite* 19 Arsenic trioxide ride) 70. Cholesterol dine* 114 Irans-Dichlorobu- 154 Ethyl `methane- 2J(J 4.4'-Methylenebis sulfonate' chloroanilme)' 20 Aurolhiogtucpse* 71. Chromic chromate* tene 155 Ethyl Selenac 211. 4,4'-Methylenebis 21 Azaserme* 72. Chromium acetate 115. 3,3'-0ichloro-4,4'- 156 Ethyl Tellurac methylamline)' 22. Aziridme" 73 Chrysene* diamino-diphenyt 157 Elhynodiol diace- 212 4,4'-Methylened.- 23. 2-(l-Azirtdinyl)- 74 Chrysoidine* ether' tate' anilme ethanot' 75 C.l Disperse Yel 116. Dietdrin* 158 Evans blue' 213. Methyl iodide' 24. Aziridyl benzoqui- low 3 117. Diepoxybutane' 159 Fast green FCF' 214 Methyl _ melha' none* 76. Cmnamyl anthrani- 118 1,2-Diethylhydra- 160. Ferbam Sullonate* 25 A20benzene* late zine' 161 2-(2-Formylhydra- 215 W-Methyl-W'-nilrc 26. Barium chromate 77_ Citrus red No 2' 119 Dtethylmtrosamine' zmo)-4-(5-nitro-2- N-nitrosoguam 27. Benz(a)acrrdine* 78. Copper B-hy- 120 Diethyl sulfate' turyl)thrazole* dine' 28. Benzjc)acndine* droxyquinolme 121, Digiycidyt resorci 162. Fusarenon-X 2'i6. Methyl red 29. Benzo(b)fluoran- 79 Coumarm* nol ether 163 Glycidatdehyde' 217 Methyl Selenac thene* 80 Cycasm* 122 Dihydrosafrote' 164 Glycidyl oleate 218 Methyllhiouracif 30. Benzo(/)f1uoran- 81 Cyclochlorotme* 123 Dimethisterone 165 Glycidyl stearate 219 Metronidazole' thene* 82 2.4-D and esters 124 Dimethoxane* 166 Griseofulvm* 220 Mirex* 31. Benzo(a)pyrene* 83 Daunomycin* 125 3,3'-Dimethoxyben- 167 Guinea green B* 221 Mitomycin C' 32 Benzo(e)pyrene* 84. D i C Red No. 9 zidme* 168 Heptachlor 222. Monocrotaline' 33. Benzyl chloride* 85. Dichlorodiphenyldi- 126 p-Dimelhytammo- 169 Hexamethylphos- 223 Monuron* 34. Benzyl violet 4B* chloroethane azobenzene* phoramtde* 224 5-(Morpholino- 35. Beryllium* (DDD) 127. p-Dimethylamino- 170. Hycanlhone (mesy methyl)-3-[(5- 36. Beryllium oxide* 86. 1,1-Dichtoro-2,2- benzenediazo-so- late)* nilrofurfuryh- 37. Beryllium phos phate* 38. Beryllium sullate* bis(p-chlorophenyljethylene (DDE) dium sulfonate 171. Hydrazine* 128 lrans-2-((Dimethyla- 172. Hydroqumone mino)methylami- ,, 173. 4-Hydroxyazoben- dene)-amino]-7 oxazolidinone 225. 1-Naphthytamine 39. Beryl ore* 87. DDT* noJ-5*[2-t5-nrtro- zene 226. Native carrage. 40. BHC technical 88. Diacetylaminoazo- 2-fury|)vinyl)- 174 8-Hydroxyquinoltne ans* grades)* 41. Bis(i-azindinyl)- toluene 1,3.4-oxadiazote* 175 Hydroxysenkirkine 227 Nickel carbonyl 89 AI.N-Diacclylbenzi- ' 129 3.3'-Dimethylbenzi- 176 liwtono! 1.2.3- 220 Nicknlnmnc' moiptiOl'fiopho-.- rime' phino siilluli)' HO Di.ill.ito' rimo' rrl)|iynmi>' f.tO DmKitliylc.Kli.tiiioyl til lum (tnxli,m' ??0 Nn kill nxriln' ?30 Nu kcl pnwih-r1 42 Disfc lilotoaitliyl) 91 2,4 Oi.immo.uii'iolo cliliriKk'* 1/11 iron xli-xtiio* 231 Nil k(>l Mill .ulliil ether* (sulfate) 131. 1,1-Dimelhylhydra- 179 Iron oxide 232 Nindazote' 43 1,2-Bis(chloro- 92 4,4'-Dinminodi- zme* 100 Iron-sorbilol-citric 233 5 Nitronco- melhoxy)ethane' phenyl ether' 132 1,2-Dimethythydra- acid complex naptilticne' 44 1,4-Bis(chloro- 93 1,2-Diammo-4-ni- zme* 181 tsatidme' 234 4-Nitrobiphanyl methoxymethy!)- trobenzene 133 Dimetbylmtrosa- 182 Isonicolimc acid 235 Nitroturaldehyd: benzene* 94. 1,4-Diamino-2-ni- mme' hydrazide* semicarbazon 45. Blue VRS' trobenzene 134 Dimethyl sutlate* 183 Isopropyl alcohol 236 1-{(5-Nilro furfur. 46. Brilliant blue FCF* 95 2,6-Diammo-3- 135 Dmilrosopentame- 184 Isosafrole* dene)aminoj ; 47. 1,4-Butanediol di- (phenylazo)-pyn- thylenetetramine 185 Jacobme imidozoliomoi methane-sulfo- ' dine (hydrochlo 136 1,4-Dioxane' 186 Lasiocarpine' 237 N-|4-(5 Nilro-2- nale (Myleran)' ride) 137. 2,4'-Diphenyldi- 167 Lead acetate* furyt)-2-th'azo 4J8 /3-Bulyrolactone* 96 2,4-Diamino- amme 188. Lead arsenate acetamide' 90S1574 CANCER RESEARCH VC RSV0033795 Evaluation of Carcinogenicity of Chemicals Table 3 ~ConluMtrd 2JB Nitrogen mustard (hydrochloride)* 239 NitrOqpn mustard N-us Hit* (liydio- chlondet* 40 Nurosoelhyturea* H Nilrosomethylurea* 242 W-Nil roso-N-met hyI- urethan* 243 Norethisterone* 244 Norethisterone ace* tale* 245 Norethynodrel* 246 Norgestrel 247 Ochratoxin A 248 170-Oestradiol* 249 Oestriol 250. Oeslrone' 251. Oil orange SS` 252. Orange I* 253. Orange G 254. Oxazepam* 255 Oxyphenbutazone 256 Parasorbic acid* 257. Patulm* 258 Penicillic acid' 259 Phemcarbazide' 260 Phenobarbital si dium' 261 Phenoxybeozarmne' 27g Propylttvouracir 262 Phenylbutazone 280 Pyrimethamine' 263. m-Phi'iiylrni'di- ?fi 1 p-Quinnim .itiiuic (hydro 21!J (Juintozuite* chloride) 2B3 Reserpine 264 p-Phenylenedt- 284 Resorcihot amine (hydro 285 Relrorsme* chloride) 2B6 Rhodamme B* 265. N-Phenyt-2- 287 Rhodamme 6G* naphthylamine* 288 Riddellnne 268 Polychlorinated bi 289. Saccharated iron* phenyls* 290 Satrole* 267 Ponceau MX* 291, Scarlet red 268 Ponceau 3B* 292 Selenium com 269 Ponceau SX pounds 270 Potassium arsemte 293 Semicarbazide (hy 271 Potassium bi*(2-hy- drochloride)* droxyethyl)-di- 294 Senectphylline thiocarbamate* 295. Senkirkme 272. Progesterone* 296. Sodium arsenate 273. Pronetalol hydro- 297. Sodium arsemte chtoride* 298. Sodium dichromate 274. 1.3-Propanesul- 299 Sodium diethyldi- tone* thi ocarba mate 275 Propham 300 Sterigmatocystin* 276 /3-Propiolactone* 301 Slreptozoloctn* 277. n-Propyl carba 302 Strontium chro mate* mate* 278 Propylene oxide" 303. Styrene oxide 304 Succinic rinrio* anhy- rtif. Si n tan r 300 Sudan H* 307. Sudan ttl 308. Sudan brown RR 309 Sudan red 7B 310 Sunsel yellow FCF 311. 2.4.5-T and eslers 312 Tannic acid* 313 Terpene polychlon- nates* 314. Tesloslerone* 315. Tetraelhyl & tetramethyl lead 316 Thioaceiamide* 317. 4,4'-Thioamline* 318. Thiouracil' 319 Thiourea* 320 Thiram 321. o-Toluidine (hydro chloride) 322 Trichloroethylene* 323 Trichtorolrielhy- lamtne hydro chloride 324 Triethyler.u glycol diglycidyl ether* 325. Tris(aziridmyl)-p- benzoqutnonc' 326 Tn'.(t-firintlinyl)- litui'.plum- iixmIp J27 fris(t-nziudlnyl)- phosphme sullide* 328 2,4 6-Tris(1-aziridi- ny!)-s-triazine" 329 1,2.3-Tris(ch!oro- me1hoxy)-pro- pane* 330 Tns(2-melhyt-1- aziridinyl)phos- phine oxide 331 Trypan blue* 332 Uracil mustard* 333 Urethan* 334 Vinyl cyclohexane 335 2.4-Xyiidine (hydro chloride) 336 2,5-Xylidme (hydro- chlonde) 337. Yellow AB 338 Yellow OB* 339 Zeclran 340 Zinc chromate hy droxide* 341. Zmeb 342. Ziram I Asterisk, chemicals for which there is some evidence of carcinogenicity in experimental animals only (see also text, p 681). food additives or chemical residues in food are concerned, the value of experimental results to predict a similar effect in humans has been accepted as valid. The criteria used in the preparation of the draft mono graphs, in judging the adequacy of the data and in evaluat ing the carcinogenic risk of chemicals to humans, were first fabltshed in 1971 and. with minor modifications, have ^een adopted by all the working groups whose delibera tions have resulted in the first 16 volumes of the IARC monograph senes Adherence to thts basic uniform back ground and maintenance of a certain rigidity in observing the rules set out in the preamble to the monographs permitted a relative uniformity of the evaluations formulated by the working groups The growing success and overall acceptance of this program have certainly not prevented suggestions and criti cisms Criticisms mostly refer to the fact that, except for the few instances in which an association between exposure to a chemical and occurrence of cancer in humans has been clearly confirmed, the monographs do not give a clear indication as to whether exposure to a chemical does or does not represent a hazard to humans because no attempt was made to evaluate the potential human risk In most cases, in fact, the monographs only evaluate the carcino genic risk of chemicals to experimental animals without making any attempt to interpret the results in terms of a possible risk for humans. It was for these reasons that an ad hoc working group, jointly called by IARC/WHO, was convened in October 1977 in Lyon to update and revise the criteria on which the carcinogenicity of chemicals to humans and/or experimen tal animals is assessed and on which the evaluation of the possible carcinogenic risk that they may represent for humans is made. The report resulting from this meeting will appear as the "Preamble" of Volume 17 of the IARC monograph senes which is presently in preparation (38) and will replace the introductory section called "Background and Purpose of the JARC Program on the Evaluation of the Carcmoge c Risk of Chemicals to Man.' which appeared since 1971 with only minor modifications in all the 16 published monograph volumes. We would like to mention briefly here only the more significant changes that will henceforth influence the formulation of the evaluations, and the reader is referred to IARC Monograph. Volume 17. for the text m its entirety. While it was recognized that no adequate criteria are presently available to interpret experimental data on carci nogenicity directly m terms of their carcinogenic potential to humans, it was also noted that extrapolations to a possible human risk can be. reasonably approximated by utiJizmg data from appropriate animal tests. These data, however, may represent different degrees of evidence, this drawback being mainly due to our present insufficient knowledge of the mechanisms of carcinogenesis "Strong evidence" of carcinogenicity is indicated by the unques tionable production of malignant tumors, white "weak evidence" of carcinogenicity reflects the qualitative and/or quantitative limitations of the experimental results of which a particular case could be. for instance, the induction solely from benign tumors in mice In the presence of ap propriate experimental carcinogenicity data and in the absence of adequate human data, it is reasonable to regard chemicals for which there ts "strong evidence" of carcino genicity as if they were carcinogenic to humans. Chemicals APRIL 1978 3061575 883 F L Tomatis et a! for which the<e rs weak evidence of carcinogenicity in ex perimental ammals will, in general, require more experi mental and epidemiological investigation. It was recognized that there are no acceptable methods lor quantifying the possible errors in making an approxi mate quantitative evaluation o! human risk at some given exposure level on the basis of data that provide strong evidence of carcinogenicity in experimental animals The limited data available, however, suggest that such a rela tionship may exisl. at least within certain classes of carci nogenic chemicals, provided that account is taken of the nature of the chemical concerned and of the possible ol the moncQUuhn Wiitiout fhov roirorfnc priifpsuonat dtivicc ,mrf sui't the monograph program Could no! have been implemented and continu Or J Cooper and Or S 5<egei, Project Oncers ol the Nat-ona* Institute o* the United Stales we*e instrumental m initiating and mmnia.r active mln/rsi and support in ih*s program Wc would tWso tki io ti>nnk K E MrColnb ol SH* intnrnAtmnriJ unf Dr J R W.isvmt ol P*i twirnw*. tal Mutagen information Center. Oak. Ridge National laboratory Tor r> cHorls in providing data particularly on produchon and use ol chemic and on their mutagenic and teratogenic effects, and Dr. v Ponomarv Dr T Kuroki. and Dr l Gnciutc tot their valuable contributions at monograph meetings We also Thank D MioUon and 1 PelerschmiU (or assistance in bibliographical research C Partensky and E Ward lor technical and r editing of Ihe monographs A Anderson MJ Ghess, end R Johnson secretarial help and R Johnson l Kitchen and E Perez lor assistance the preparation of this manuscript physiological, pharmacological, and toxicological differ ences between (he test animals and humans References More consideration than in the past is also given 1o indirect tests, most of which do not have the production of neoplasms in ammals as the end point and are generally referred to as "short-term" tests. These lests are proposed to be used, (a) for the prediction of potential carcinogenic ity when other carcinogenicity data are absent, (b) to contribute to the setting of priorities for chemicals to be tested in animals, (c) for the identification of active frac tions from complex mixtures containing carcinogens, (d) lor the identification of active metabolites of cacmogens in human body fluids, and (e) to help elucidate mechanisms of chemical carcinogenesis The last section ot the monographs, which was originally headed "Comments on Oata Reported and Evaluation," and comprised 2 subheadings. 1 for experimental data and 1 for human data, will now be called "Summary of Oata Reported and Evaluation", it will have 3 sections, > e . a summary of experimental data, a summary of the human data, and the evaluation The evaluation section will lake into consideration all ol the data in the monograph, partic ularly the summarized information on ammals and humans The revised criteria for the evaluation of the carcinogenic risk of chemicals to humans have already been applied by the IARC working group that finalized the monographs scheduled to appear as Volume 17, which considers some W-nitroso compounds (38) By applying the new criteria lor the evaluation of the carcinogenicity of chemicals as they are described in the new preamble to the monographs, as well as acquiring further carcinogenicity and related data on chemicals and new knowledge on the mechanisms of carcinogenicity as it may become available, we hope that in the absence of epidemiological data a more clear distinction can be made between chemicals for which there is or is not evidence ol a possible carcinogenic effect in humans We hope that in this way the cnncal analysis ol the experimental and lnmi.ui data nntl Ihe ensuing ovnlualinns ol onvuonnu'iilal <liriiiii .il'. will ni,ik<> lullin' IAIU'. mono graphs more usolul in assisting national and international authorities <n lorniiil.itiiuj deusions concerning preventive measures. Acknowledgments To list all the 177 investigators irom Pie 24 countries who have paritcpaled in and contributed to the IARC monograph program ts impossible Although this article retlecls our personal views and opinions, we express our deep gratitude to alt the individuals who participated in fhe preparation t Aglhe C . and Tomahs. L Evaluation of the Carcinogenicity ol Envuc mental Chemicals and the Possibility of Cancer Prevention in Homburger fed ) The Physlopaihotogy ol Cancer Vot 2,pp 35 3` Basel S Karger AG 1976 2 Aglhe. C and WHbourn, J D IARC Programme on the Evfiuation Carcinogenic Risk of Chemicals to Man fn P Bucalossi U Veronc and N Caseineili (eds Proceedings of the Eleventh internal^ Cancer Congress, Florence. 1974 Voi 3. pp 108-113 Amsterda Excerpla Medica 197$. 3 Boyland. E The Correlation pf Experimental Carcinogenesis and Car i in Man Progr Exptr Tumor Res.. IT 222-234 1969 4 Cairns J The Cancer Problem So Am 233 64-78 1976 $ Carcinogenesis Program National Cancer Institute Survey of Co pounds Which Have Been Tested lor Carcinogenic Activity. Put Health Service Publication No 1*9.1968-1969 Washington D C U Government Printing Office, 1971 6 Carcinogenesis Program National Cancer Institute Survey OT Cc pounds Which Have Been Tested lor Carcinogenic Activity. Put Health Service PubUeaUon No 149 1961-1967 Washington, 0 C U Government Printing Office. 1973 7 Carcinogenesis Program Notional Cancer Institute Survey of Co pounds Which Have Been Tested lor Corcmogernc Activity. Put Health Sendee Publication No *49 1970-I97t, Washingiqp, 0 C U Government Printing Office. 1974 8 Carcinogenesis Program National Cancer Institute Survey ot Co pounds Which Have Been Tested for Carcinogenic Activity, Pub Health Service Publication No 149,1972-1973 Washington. 0 C U Government Printing Office, 1976 9. Doll. R Prevention of Cancer Pointers from Epidemiology Nufl> Provincial Hospitals Trust, 1967 10 Dctf.R Strategy for Deiecuon of Cancer Hazards lo Man Nature 2 589-596 1977 11 Haddow, A Proceedings of the Nmeth International Cancer Congre Tokyo, J'pen. *966 UICC Monograph Ser., 9 Mf-tte, 1967 t2 Hartwell, J L Survey of Compounds Which Have Been Tested Carcmogemc Activity, Public Health Service Publication No 1*9 Wa inglon, 0 C U. S Government Printing Office, 1951 13 Niggmson, J Present Trends in Cancer Epidemiology Can Can*. Conf.fl 40-75.1968 14 Higginson. J A Hazardous Society? Individual versus Community F sponsibility m Cancer Prevention Am J Public Health. 6 359-3` 1976 !$ IARC Information Bulletin on Ihe Survey ol Chemicals Being Tested ' Carcmogenicily. Vol 1 Lyon. France International Agency lor Resear on Cancer, 1973 16 IARC Information Bulletin on the Survey of Chemicals Being Tested Carcmogenicily. Vol 2 Lyon France International Agency tor Resea on Cancer 1973 t7 lAttC Ifitnimilicm IliNj|ln on Ihn Survey of Chontlt nK Ehilng 1 osUmI Cnirliiri|nnli Uy Vnl 1 Lyon Ft.nub tiiljitiiiilimiil-Afyiir y fin U-wm tin Tim< r I l *4 16 lAtlL Intinin iluin Hulli'llrt on Ou> i*tiv>y of Uuunli iiti Eji4ni| f *n|iHl CflrrlnngiMMCilv. Vol 4 Lyon Frpnrn Inlnmnllmiat Act*iiry fin n*r*i rm Cam i * <*'74 19 IARC Informahon Quilehn on |r>e Survey of Chemicals Being Tested Carcmogenicily. Voi 5 Lyon. France International Agency for Resea on Cancer 1975 20 IARC Information Bulletin on the Survey of Chemicals Being Tested Carcmogenicily, Vol 6 Lyon France International Agency for Rases on Cancer 1976 21 IARC Information Bulletin on (he Survey of Chemicals Being Tested Carcmogenicily. Vol 7 Lyon. France International Agency for Resoa on Cancer. t97B 72 IARC Monographs on ihe Evaluation of the Carcinogenic Risk of Chi 90S1576884 CANCER RESEARCH VOL RSV0033797 vsltidlion ol Catctnnycn'cily ot Chemicals teals lo Man Vo' < Somt Inorganic Substances Chlorin.iti'd Hydrocar bons Aromatic Aminos, At Nitroso Compounds and Natural Products Lyon France International Agency lor Research on Cancer. 1972 77 (ARC Monographs on the Evaluation of the Carcinogenic Risk of Chem icals to Man Vol 2. Some Inorganic and Organometatlic Compounds Lyon, France International Agency tor Rcsearrh on Cancer, 1973 2* IARC Monographs do the Evaluation of the Carcinogenic Risk of Chem icals to Man Vol 3. Certain Polycyclic Aromatic Hydrocarbons and Heletocychc Compounds Lyon, Franca International Agency 1' Re search on Cancer, 1973 25 IARC Monographs on lha Evaluation of the Carcinogenic Risk ot Chem icals to Man. Vol 4, Some Aromatic Amines, Hydrazine and Retated Substances. N-Ntl-oso Compounds and Miscellaneous Alkylating Agents Lyon. France International Agency for Research on Cancer, 1974 26 IARC Monographs on the Evaluation of the Carcinogenic Risk ot Chem icals lo Man. Vot 6, Some Organochforme Pesticides. Lyon. France International Agency for Research on Cancer. 1974. 27 IARC Monographs on the Evaluation of the Carcinogenic Risk ot Chem icals to Msn, Vol 6. Sen Hormones Lyon. France International Agency lor Research on Cancer, (974 28 IARC Monographs on the Evaluation ot the Carcinogenic Risk ot Chem icals to Man Vol 7, Some Anti.thyroid and Related Substances. Nitrelurans and Industnal Chemicals. Lyon, France International Agency tor Research on Cancer, 1974 29 IARC Monographs on the Evaluation ot the Carcinogenic Risk ol Chemical* to Man, Vot 8. Some Aromatic Aro Compounds Lyon, France International Agency tor Research on Cancer, 197S 30 IARC Monographs on the Evaluation ot tha Carcinogenic Risk ol Chem icals to Man, Vo) 9 Some Aaindmes. AT-, S- and O-Mustards and Selenium Lyon, France International Agency lor Research on Cancer. t975 31 IARC Monographs on the Evaluation ol the Carcinogenic Risk ot Chem icals lo Man. Vol 10, Some Naturally Occurring Substances Lyon. France International Agency for Reseerch on Cancer. 197S 32 IARC Monographs on tha Evaluation ot the Carcinogenic Risk of Chem icals to Man. Vol It. Cadmium, Nickel. Some Epoxides, Miscellaneous Induslnal Chrmicals and General Considerations on Volatile Anaesthet ics Lyon. France International Agency for Research on Cancer. 1976 33 IARC Monographs on the Evaluation ot the Carcinogenic Risk ol Chem icals to Man, Vol 12, Somt Carbamates, Thncaibsmates and Carbazides Lyon France International Agency tor Research on Cancer, 1975 34 IARC Monographs on the Evaluation ot the Carcinogenic Risk of Chem icals to Man, Vof 13 Some Miscellaneous Pharmaceutical Substances Lyon, France International Agency lor Research on Cancer, 1977 35. IARC Monographs on tha Evaluation of the Carcinogenic Risk of Ch*m- fitly In M.in. Vof 14 Aybriliis Lyon ( Mnru Inlrriijtioml Ayi-ucy for H"SCVCh on Cancer 1977 35 IARC Monographs on Ihe Evaluation ol the Carcinogenic Risk ot Chem* teals lo Man Vol 1$, Some Fgmiganis Ihe Herbicides 2 4 0 and 2 4$. T Chlorinated O'bentod'oxms and Miscrilanroim tnduslnal Chemicals Lyon, ri.mcr Inlernnlconnl Agency for nosti.neli Oh Cstm.cr 1977 37 IARC Monographs on the Evaluation ol the Catctnogemc Rtsk ot Ch*m> tea's to Man. Vol 16 Some Aromatic Amines and Related H<iro Com. pounds H*tr Oyes Colouring Agents and Miscellaneous Industrial Chemicals Lyon. France International Agency lor Research on Cancer. 1970 39 IARC Monographs on the Evaluation ol ihe Carcinogenic Risk o< Chem icals lo Man Vol 17 Some N-Nriroso Compounds Lyon. 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New York Cold Spring Harbor Laboratory, 1977 4$ Weiss. W Chtoromethyl Ethers Cigarettes Cough and Cancer J Occup Med . T8 T94-199 1976 46 Wetss, W . and Boucot. K R The Respiratory EKeels ol Chloromethyf Methyl Ether J Am Med Assoc 234 1139-1142 1975 47 WHO Filth Report of the Joint FA07WH0 Expert Committee on Food Addibves Evaluation ol Carcinogenic Hazard of Food Additives World Health Organ Tech Rept Set ,, No 220 1961 t 46 WHO Report of a WHO Expert Committee Prevention of Cancer World Health Organ Tech Rept Ser . No 27d, 1964 49 Wynder, E L Cancer Prevention A Oueslton of Priorities Nature 268 284, 1977 50 Wynder E L , and Gon. G B Contribution of the Environment to Cancer incidence An Epidemiological Exerose J Nil* Cancer Inst 58 825-832 1977 APRIL 1970 9051577 RSV0033798