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p. and Carretti, D.: La cance ale: nuove prospettivc alia ~ uro 4i vinile. Gli Ospcdali \ L. and Chieco, P.: Insorgsr.zi lito a soiaministrazlone per Jli Ospedali della Vita, 1875, * I vinyl chloride, in "X Inter} 1970, Abotr. vol. 29. , A.: oncogenic response of rl chloride. Cancer Res., :o, p#: "Subcutaneous sarco ition of chromium orange and ial Symposium on the Biologic<urs, Bologna, 1973, in Adction and Characterization, 4, Excerpta liedica. ,'t study of bronchial earcino pigments. Brit. J. Ind. OCCUPATIONAL CHEMICAL CARCINOGENESIS C. MALTONI Tables 1 to 18 i | RSV 001284-4 t RSV 0012845 Table 1 CAUSES OP INCREASED ONCOGENIC RISK IN HUMAN ENVIRONMENT I - Concentration of oncogenic agents already present in the surface of the Earth. II - Surfacing of oncogenic agents from the depth of the Earth, III - Production of new potentially oncogenic compounds by chemical and petrochemical industry. Table 2 KNOWLEDGE AND PACTS WHICH MAKE URGENT A. NEW APPROACH TO THE PROBLEM OP INDUSTRIAL ONCOGENESIS I - The potentially oncogenic agents in human environment are progressively increasing, II -- Different oncogenic agents may have additive effects. III - Changes produced by oncogenic agents are largely irreversible. IV -- Oncogenic agents may exert their effects on different organs and tissues and widely affect the target organs. V - A large part of the natural history of tumours take place without any clinically and sometimes otherwise detectable pathological changes. VI -- Cancer is not a reversible disease. 137 RSV 0012846 \ Table J Experiment* Rtt end BIS t Sxaoaar^ by inhalation to VC In air, at 30,000, 10,000, 6,000, 2,500, 900, 2;0, 30 ppa,, *4 hr*. dally, $ days weekly, far $2 week*. Results after 1)} weeks (end of the e*o*Tlnrat). CMU23 ARB ThEATVERT Ah IB AW (SFRA GUE-DAXLET rats) Corrected Petal number (a) 1 VC 30,000 PP. 11 VC 10,000 ppm. til VC 6.COO pnz. tv VC 2.300 PP*. 4 VC 900 wv. VI VC 290 pen. Vi! " VC 30 ppa. ------------mr Ho treabeeot $0 6? 72 74 61 67 64 68 Total 541 SO 61 60 59 59 59 59 58 475 tv3bol gland -Inessa (b) no. * 35 58 Average latency (weeks) 43 16 26 50 7 12 62 2 3 - 47 m 79 64 - _ - Nepheoblaatoaas (e) Average Re. r latency ,11ae . (weeks) -. - 58 59 47 65 6 10 74 47 83 6 10 60 12 26 - 135 _ - AHUAlS SITH MMOIAS Aj^rioTafeo^aa Liver (d) Other silt* SubCUt* stout ii Skin c*x clnoass Hopatooua Brats neu lianaty rsblaetoZ cirelnj as as Other tyj* .iS'T.) Avtraft Ro, * Utin:; Ro, tt* . no. ro. Ro. Me. Re. Be. fetal (*) Ro. 18 10 9 15 13 22 M 22 7 12 47 12 _ 65 - 53 1 ( 64 3 (f 70 JJJL 78 3 <h 81 2 <1 79 a (i 135 1 (a - 15 . 4 1 7 1 t 12 3 1 t 1 4 1 11 _ 1 1 2 ) _ _ 7 _ _ 27 (o) 51 7 3 4 (P) 38 .1 8 (e) 31 5 1 3 lr> 32 1 3 (a) 22 _ 1 2 <t> 16 m 2 7 <) 10 m . 10 (v) 6 15 8 64 206 ) Alive antaale after 24 week*, when the first tumour (s tycbal gland carelDocs) mi observed, The percesioges are referred to the corrected maker. b) Hetastaaee to lung. e) Ketaataee* to liver, lung, spleen and brala. S) Vethatste* to lung. c) 1 lung angiosarcoma. f) 1 intrubdonlnal angiosarcoma (next to liver)} t ngiaereoe of the lipaj 1 anglsaarceeia of the noae, l) 1 angiosarcoma in suboutoneeua fibrosing anglon*) 1 eeslfylnc paraurlculer angiooarcooai I Intrabdoaisal angioaarcona (neat to liver), h) 1 ossifying ongiesarcons of reck; 2 lntrabdoslnal lutcioaarcoaaa (l next to spleen and 1 next to ovary), 1) 1 angiosarcesa of uterus; 1 lung angiossreoaa. 1) 1 InlrnbdooJnnl ancionarearea (next to spleen)} 1 Introthoracic ossifying angioeorco**. a) 1 intrubdaalnnl diffused anclosarcomo. n) Several cases of breast flbreedehoBOe, adrenal And pituitary tuaeurs (generally adenosee) have net been eeaeldertd, since their distribution In Iht different groups deec not vory, o) 7 Symbol gland edenomss; 1 nkin eQuonoue csrclnoaa; 1 (ubeutentoue flbroangtom*} 2 aanaary eerclnoasa; < hepatic angleaaj 1 bepatos*} 1 ovarian anglosai 11 foreatoeach papillosos; 1 brain neuroblastoma; 1 Harlerlan gland earelnons. p) 2 lyabsl gloni odcnosuio; 1 ovarian cyotosdeneearelnona; 1 ncurlltiuneaa, q) e Zynbsl gland adenoaas; 2 hepatve and 1 peritoneal angloaaet 1 salivary gland adcnetotcinosa, r) 1 2)>ba1 gland odencevn; 2 epcmlynoena. s) 1 pulaoi>ry flhro-.arcocu; 2 )yn|>ica::. t) I lymba) gland O'lrnaea} 1 lyc-p-iDna, u) ) Syrhal i;1m4 alcnoiw.in; 1 nibeutan'-ous eng toper! cl toaa j l uterine adenoenrein'ons (1 with atr.'OoatouB cosponcnt), v) I iuvus'ivr antl:on.i rf Iraki) gjueili 1 subcutaneous fltircRnrcorn; 1! nrrl toncul f l brotinr serene: 2 uterine ed enoearclnoBO* (I l uleiirv i rtonv>:::'c..nu: 1 r.wirinn 11 Pro ju-com ; : |iblfflornry ;hreeaayoo<,.reonn>. 1 lynphbmc. i) Several neictrii; r.,l>i ? jr non1 tunouic. '1th r.oreoratoue component); RSV 0 0 1 2 8 4 7 if i h*--- > >- - i!! "!^"^;:";:":i,f rs'issjsr"1 "'""< *'* ^s:rs"',?s^sr *,"TM" '"' " i! i ssssss "*"* -*-TM~. ",'it'.ssr'---I * ><* ----,...)................... " papiiioMo; ;';TMr;us".'M"n;::ri 2 ""t > .... i H; S= 3 1 FUlaonar? flbrocnre| 3 lynphena*. t) 1 Symbol glar.d odenoaa; 1 lynphoaa "> \ > - --- 3 uterine r--< -*> Mnm. ee.P#n.nt)< 2 ut*rin* 1^. ,, .lth w.,,,,. ,,opon,nt): Table 4 Experlacnt BT4 I Esaoaure by Inhalation to VC in air at 10,000, <,000, 8,500, >00, 250, 50 pin., for 4 bra, dally, 5 daya weekly, for >0 weeka. netulta after 81 week* (end of the oxr'rlacnt). CROUPS anhials (crass mice) Total Corrected auaber (a) TREATMENT ------------j----VC to,000 ------------n------------ 1 ----------irV VJ --nt 0* 30 30 30 30 30 30 ? JO 60 10 60 10 60 30 60 30 60 30 60 Hf, <? H 22 2B 50 26 28 54 23 30 S3 20 29 ?S 29 29 58 2T 30 57 67 1< l Lung tuisoure (b) Aver*** No. 5 latency a Hnt (neikp) ANlNAlS WITH Tt0UH3 Eaeoary careinonas (el Liver an- Vascular tunouro gioiarccaao of other type er.fi/or alt* Epithelial tuaoura of the akin Other type and/or elts Avtragi He. litmey * tipte 4 (wrnkB) He, Ho. Ho. Ho. Total (a) He. 35 70 36 J 70 30 57 38 43 36 66 41 33 57 45 2 3.5 51 6 f 44 13 47 8 26 9 30 7 24 11 ?* 12 33 . 31 33 35 37 39 43 m 0 _____L <d) 3 (a) 2 trl 16 5 9 All______ 6 SAL- 4 Jsi. 39 11 12 eo 3 (a) 2 to 31 II 16 All______ 1 1 JaL- )11 22 (h) 2 -Lsl_J Jil . 40 1 13 <1> - ) () 16 _ lm 7 _(yi- cu total 260 250 50 2)0 2*1 47 184 - 60 - - 47 64 15 20 270 -o a) Alive a.ilaala after IS weeks, when the firet tumour (a aaraenry earclr.wa) was observed, the percentagea ere referred to the eerraetad ituaber, b) Adangnos, eonc of which undergoing alienout traaforaetion. ) In fannies. Adenocarcinoaa* frequently with area* of aquunoua aetaplaela. d) 3 subeutancoue onfianoa; 4 liver flbroenglooes) l heart flbroangloaas I ossifying Intaraeapuler engloss. e) 1 subcutaneous enf;ioaareoa| 2 liver flbroenciocasj 4 liver angloatna; > renal flbroangloaai 1 thymia angloBa, f) 3 aubeutnneous arpiorurcoosoj 1 eubeutnneoua angieaai 3 liver angloaaai 2 lntrabdoainal anglosarcoaasj 2 renalangiosarcomas | 1 lung angleaa. rl 2 subcutaneous oneiossreosast 1 subcutaneous flbrosngiomai 1 aubeutaneous angionoj 4 liver fibroangioaaei 1 liverangloaai) lntrabdoainal nngie* aareoeos; 1 lntrabdoainal fibreonglonn; 1 renal angiosareooaj 1 testicular fibroanglosai I angloaa of the oaeeuai 1 lung flbroongloDai 1 lung angioma. h) I subcutaneouc anglom; 6 liver fibroanglcmne| 10 liver orglaaaa; 2 lntrabdoainal ongioeeroowatj 1 ovarian angloaai 1 aeraul angloaai I lung angiosa. i) I aubrulaneoua ancinaureeaei 1 subcutaneous fibroergiaaai 2 aubcutaaaoua angloaait 2 liver flbroangloaaii 3 liver aniloaaai 1 lntrabdoainal angloaat 1 ovarlon angioma) I lntrathoraelc flbroanglonaj I angloaa of the tatereeapular fat pad. 1] I angiosarcone of utorua. a) 2 squanoua carctneaea; 1 invailve acantboaa. n) ; aquaaoua carctaoaasi 1 aeonthoaa. a) l equanous carelneaai 2 acanthomas. i p) I aeonthoM. q) I shin odcnoearcinaani 1 besalioaa. I rj I lynbal glar.4 sdenoan; 1 feresteaaeh paplllona. j a) 1 eubcuteneeua lelaryoaarcoreai t fertstoaaeh paplllorsaj 1 Harderlan glare! odeneaaf I lynphoaa. J t) 1 forestoaach popllleaai 1 parotid gland alxed tunour. uj i Zynbal gland oder.ona. y) 1 tyr.bal gland odenoaa) t Leydig cella tunouri 1 lyaphoaa. a) 1 parotid gland edenoeareinoaa. y) I subcutaneous lelaayeaarcoaa; 1 odenoaa of colon) 1 ovarian carciaoaa; 1 leleayeaareoaa of uterus; J lyaphoaoa. a) Several eaeeo with 2 or aore tuaoura. f j i Ii RSV 0 0 1 2 6 4 6 table $ Experiment ME t Ercoaury by Inhalation to VC Is air at 10,000, 6,000, 2,$00, 5<X), 2*0, $0 ppa., 4 bra, daily, 3 daya weekly, for JO *ffki. Decalts after 10$ weeks. CROWS TREAfUQtt UtOUU (cou>e:i hakstbk) Total Survivors Skin wliver eboepitbe figlevt?" lioaae and C09IP baaalioaae fal Po Bo. s VC 10.000 009. 11 VC 6.000 otM. Ill VC 2,$oo -pea. Iv 1 VC 500 OBO. V VC 250 ppm. Vi VC 50 nt. Vll He treabeent 35 32 33 33 12 13 70 - . 1 -6 12 -? 23 -3 -6 -2 total 260 1 1 33 MBULS 1TII TUKOORS lyapboaaa Porertonacb epithelial tomn (*) Be. Ro, Ro. 1- 22 7 _ 1 10 _1 _1 7 2 1 _2 4 B 34 a) Several eaeee with ecnntbeeie and eoae undergoing aallgnant trasforaatlen. b) Pepillocea, acanthonae, eon# Of which undergoing eolignant traeforMtlon. c) 1 aabeutaneoua ongiooa; \ gall-bladder edenoeartihoo*. 4) 2 hepatoaae; 2 liver llbnaipMu; 2 liver ugttaai; 1 billduct* adcnocerclBoaa, e) 1 hepatoma; 1 liver flbroangioar; 1 liver nnglcaa, f) l aubcutaneeue angioma; 1 bronchial earclnoaa. g) Several animals with 2 , r sere tunoure. Other type and/or atte He. 2 <e) 7 (d> 3 2 If) m 14 total (.1 He. 10 12 12 6 10 5 55 table 6 Experiment Bill : Erroaare by ingestion (steaaeh tube) to VC In olive oil, at 30.00, 16,6$. J.U ng/Kg body wi*nt oaee daily, 1-5 dsys weeKly, for $2 weeks. Besulta otter 84 weeks. CROUPS Aid) ffiZATKQIT jumui (SPSUCUE-DATirf rats) total Survivara I VC 50.00 ag/Kg 80 25 11 VC 16,65 agAg 80 33 111 VC 3.33 aAg IV Contrdb olive oil 80 80 30 J7 Sysbal gland carcinOBaa AHIKAU WITH TUKC'JBS Nephrablastomas Ann pureft*** liver Other Be. Re, Ha. Ro. Other type and/or site (b) No, _ _ 8 i (a) 3 (e) 1 15 _ __ - - -- - Total Re. 11 (d) 7 - Total 320 134 1 1 13 i 3 18 a) 1 thymus sngtoesreosa, b) Several eaaea of breaet flbroeder.onea; adrenal and pituitary tumours (generally adenoaoe) have Bet bees considered, einee their distribution in the different groups does not vary. e) 1 tsoarr earemoaa; 2 fereetonaeh porllloaea, d) 1 aniaal with 2 tuaoura. 140 RSV 0012849 10,000, <,000, 2,$00, o*ey, for 30 tiM,, ItH IUC0UKS iphoane (fo. Poreetaeaeh epithelial tuaaure (b) Other type and/or elte So. Pa, total (*) Vo. -4 t7 1 10 17 12 2 (e) 7 (d> 1 (e> 2 It) 14 _ 2-_ s itlon. ilea. 34 U !9 UeuxiMit, Table 7 ficperdaaat ST) < BroomiTo by inhalation to VC In air at 10,000 and <,000 ppa. of breeders, 4 ftrs, daily, for 1 weak (fraa i2th to iflth day of pregnancy), Boablta after H] aeefcs (and of the oxperlaent). ~ CHOWS tm i VC 10,000 ppn. oreedir* II VC 6,000 ppn. roedere III VC 10.000 Pl. offcertM* IV VC 6,000 ppn. hffeorince fetal All DIALS (smeuMinn bats) Total Zynbal gland carcinoma Ho. 30 - 1 30 - - 54 --1 32 3 1 146 - 5 AHVULS BITH TUMU5S Kephreblaitaaia Be. Angie Liver Ho. Other el tee Ho. - - 1 <*) - -1 - 2 (b) - - 8 () -5 Other type and/or elte Ms. Total Ho. 2 (d) 3 2 () 4m s 6 6 17 a) i intrabdealnal angioearoooa. a) 1 aubeutaneou* angloem-coso; 1 aneioearcoao of the 1 eg, c) 1 pubcutaneoua angloaarcoaa; 1 intrabdoMnal as(lewrna>, 4) 1 liver fibroangloaa; 1 liver inglona, ] 1 lyabal eland fibFeaarooaa; 1 ovarian leieayoeaj-cona. f) t iyabal eland edenona; 1 aku cereinooa; I eubcutaneoua fibroangboaa; 1 naasary earolnona. HP in olive oil, '* daily. TH TUUOURS beareoBm Dthir Rlt no. and/or elte (b) To. i <) 3 (c> -_ - Total Ho. 11 (d) 7 - -_ 3 8 f (generally adenesae) have f does sot vary. Tabic S TUSOUES PRECOtTLY CGRREIATS) TO VC CTOSUr- (BY QiKALATlCn), OK SCPER KBfTAL S03EJ.T5 JMO ilMI TtrtKWns Angiosar luaoui-s Tanours Ar.^iQU| 3ephro- Sebaceou* Squaaou: Speeioo cooae of liver brain of nas ar4 cor:as blaeto eu^meoui tuaourt rf lung leuk- and an> nne card no- of epi- carol 14S i au denta mfaia af oth*r tlepa Foreto- stcnach us papilla Baa and acantha me Oat 44 4 4 4 <+) 4 4 Bouse 4 4 4 44 4 Hanoter * <) () U> * (*) 4 Ban 4 <) (e) U) U) 141 RSV 0012850 table 9 Experiment BT10 t Ereeaure by inhalation to VC ter >00 bra., fcLloein^ different achedulea. Beaul-.a after 59 *eaka. CHOOTS AKO tmnm ahbuls (swucuE-BAbtrr Ba?31 total Survivara i rc 10.000 c?c. dWj'Sdw/^vi 11 VC 6,000 ppo. lhd/*dAe> m VC 10,000 yp, 1fcd/4d*/2Sw IV VC 6,000 fPB. ihd/d*<yS5 V VC 10,000 ppn. Jbd/Hr/2S* VI " 1 VC 6,000 ppa. Xd/1dw/25* Vll to ito 120 120 120 120 249 64 U 99 85 96 97 ISO tyabal land carcinoma* He. 4 1 4 2 - Utnu&s VITH ttttCUTG Hepweblf ttMil Angieifcreom*9 Liver Other alias Ho. Me. Ho, - -- - -' - -- - - 1 () - -- - -- Other type And/or it* He, - 1 (b) - - 1 (e) 1 <d> total No. 4 4 4 1 i 1 . Total 969 716 a) > eubcutancous a.neloau'coaa, b) 1 lyaphosa, c) 1 auboutaneoua aagieptricitotareoBm. j) 1 lymphoma. 13 - _ 1 1 17 tabla 10 Experiment Bt9 : Emo-rure by inhalation to VC in air at SO ppn., 4 hrs. dally, 5 days aeefcljr, far St erlcs. after S9 weefca. GROUPS MS) tpicsan 1 VC SB ppn. AMPULS (STRACCt-OAVLEr IUtS) total Survivor* lymoal gland eerelnooaa Ho. MURALS VITI1 TVKOVBC Raphrobla to oaa AaaieaaTteaaa Liver Other eitee Ho, He. no. Other type and/or alte Ho, total Co. 300 216 1 --- -1 II jTa trittMnt ICO 72 - - -- -- Total 400 2B9 1 - -- -1 >42 VC vc VC Ho if- total CS0C7-- AhS IHEAJVI VC 1 ft* 12 He trettotal RSV 0012851 followli* differt.it eefcedulea wiiai tuhouks | IbCloeareoBae [ liver Other altet 90, Xo. "- T----------------- ^ and/or i te Do. - Total Ho, ** 4 - 1 (b) 4 -- - 4 - 1 <A) - 1 -- 1 <e) 3 -- -_ -1 ' (d) 1 3 17 J i Table 11 Experiment FT15 t fTtrenre by Inhalation W VC ie Air, at 25, 10, 5, 1 ppm., 4 bra. daily, 5 dajro weekly, far fi weeks, keen!t after 4* weeka. MOOTS XHD TUHTUDIT I VC 25 ppm. II VC 10 pa. Ill VC 5 ppm. IV VC 1 Ppa. V Ho treatbmt Total ininu 120 -- no 120 111 120 120 111 112 120 600 97 541 Zymbal (land earelMca* Ro. AVOULS WITH TUMOURS Jlephroilstoui no. Anxipiftreesa* Liver at tea Ho. He. Other type and/or | Toal Ho. Ho. p. __ _. - - -- -~ at 50 ppo,, 4 bra, daily, -s kith rmreuas IxteioearcOBea ,VCP lo. Other oi tea Ke. and/or eite Ho. -- - Total TiO. \ -- - _ ` table 12 Experiment 9117 : Exposure by inhalation to VC lb air at 1 ppa., 4 hre. dally, 5 days weekly, for 5? ,/eeke, beeu\ta after 46 week*. CROUPS AKD irsaiho? 1 Vc 1 ppm. U Ho treataant Total AXMU.S (WISTAfl JUTS) Total Survivor* Zyatal (lad carcinomas Ho. AHIXU.S WITH TL'KOtfRS KetfU'eBla~ atone AA^teMreeiAi Liver Other sites Ho. Ho, Ho. Other type and/or el te Ho. To 1 Ho. 123 9 - - - - - - 130 89 _ _ .. _ _ _ 250 185 - ' -- - - { II I 143 > jj { RSV 0012852 ___'im \ i Table 13 Experiment BT27 ; Exposure by ingestion (stomach tube) to VC in olive oil, at 1f 0.3, 0.03 mg/Kg body weight, once daily, 4-5 days weekly, for 104 weeks. ( Results after 21 weeks. CROUPS AND TREATMENT ANIMALS {SPRAGUE-DAWLEY RATS) Total Survivors VC 1 I mg/Vg/bw 158 II VC 0.3 mgAgAw 159 III VC 0.03 rag/Kg/bw 163 IV Controls olive oil 159 Total 639 147 145 147 148 587 Zymbal gland carcinomas No. ANIMALS WITH TUMOURS Nephrobla atomas Angiosarcomas Liver Other sites Other type and/or site Total No. No. No. No. No. - - -- -- -- -- -- - - -- -- - - -- -- - - -- -- RSV 0 0 1 2 8 5 3 Vable TTT 1 / 0.03 rae/Vg/bw 1 163 147 _____ - Control} olive oil Total 159 639 148 587 - 1 - -- - _ 1 -- -- Table 14 Experiments B012 And BT2001 i Treatment! 1 subcutaneous injection of 30 mg of the compound In 1 ec of H^O. Groups Treatment 1 Chromite 11 Hoochromiun in Chromium al lumen IV Chromium yellow (Lend chromate) V Chromium orange (Lead chromate) VI Molybdenum orange (Lead chromate, sulphate and nnlvbrtatel VII Cadmium yellow (Cadmium sulphide) VIII Iron yellow (Iron oxide) IX Iron red (Iron oxide) X Control XI Titanium oxide XII Zinc chromate Animals (l) (Sprague-Dawley rate) Tumours (sarcomas at the site of injection) Total Survivors Mo.of animals Average Latency with tumours time (weeks) Histology type 40 40 - 40 40 40 - 9 8 26 27 - 78 Rhabdomyosarcomas and fibroaareomas Rhabdomyosarcomas 72 and fibrosarcomas Rhabdomyosarcomas 40 and flbroaarcoaas Rhabdomyosarcomas 47 and fibrosarcomas 40 - 36 Rhabdomyosarcomas 32 and fibrosarcomas 40 40 - 16 1 Rhabdomyosarcomas 86 and fibrosarcomas Rhabdomyosarcoma* 77 and fibrosarcomas 40 140 - _ - ~ - 120 116 - - - 80 80 - - - Ended Experiments (weeks) 133 149 137 150 150 117 143 125 134 127 (l) 5OJC males, 50^ females Ongoing experiments (weeks) 35 4 Table 15 PLAN OF THE EXPERIMENTS OH THE BIOLOGICAL EFFECTS OF STYRENE SxperinBita Species and age at ntort (weeks) 01101 Rota (U) Croups I II III IV V VI Total 0T1O2 Rats (13) I II III Total BT103 BT104 total Rats (13) I II Total Rata 03) I n Total ______________ 1 No.of animals at start Total cf $ Route 60 30 30 Inhalation Treatment Weeks Dose Stopped Ongoing Length start (weeks) 300 ppa + 44 44 60 30 30 - 200 ppm ( + 44 44 60 30 30 100 ppm + 44 44 60 30 30 -. 60 30 30 It Untreated 120 60 60 (controls) 50 ppm 25 ppm - + 44 44 + 44 44 44 420 210 210 80 80 80 240 40 40 40 120 40 40 40 120 Ingestion n 250 mg/Kg in olive oil 50 mg/Kg in olive oil controls olive oil + 37 37 + 37 37 + 37 37 80 40 4 lntrabdominel 50 mg in 40 injections olive oil (x 4) + 60 40 40 " control:olive oil + 38 38 160 80 80 80 40 40 1 subcutaneous 50 mg in olive injection oil + 80 40 40 - control; o^ve + 38 38 160 80 80 900 490 !" L .1... .... 1 . J _.......... 1. . 1 ! RSV 0 0 1 2 6 5 5 Table 16 m * jt e u 9 a c C. S V, o cn KV I/S lf> n <"A W> MA %r> 1* pa Pi *0 5 Q + 4 -t* Ml 4> Ck Ck o 4* tf] , 41 r o A 6 P. O. C. a Ffc o O o UN v CM 1 Lf\ m so SO ++ B H wS B> O-H <M O CM CM CM CM 4- 4 c ^H rl o 6*r4 IA O > > ^4^ r-*** oo rH 4* c o 6 T re a tm e n t Untreated (c o n tro ls ) c o n t r o l : oo liilv e t* 4* ac o0 c? 4* a *3 3 4 6 1 c o 4* a4 a (0 1c-4 CM S ,H o 4 tc wc ftO- O r-1 o m oPA O IoTS ri a 2 \> Ft 4* 0 O pH sr e o * ft(V o o n pa m o CM ITS CM o o o CM \e so so V3 M> O r-n G roups H c M M M H H IH 65 o r- o 00 oITS o CO ON IA o IT CO 03 r< 4O-* Ho M H *4 o so SO V r- Cm PM CD Cm CM <X> O CD g"s CM rt M M p Ho PA p~ PA p- nu v ho rUt l*o*] p n j* 2v o o p. to 4* 2 4w n 4<** C*M" ~ 4a- cV .uV3 & " o 1 ^tc BM tM t0e - CM O a ," M *H O B *- s CfCtMP* 3 H e 147 OZl I 0*.7 (1 ) 3-5 tin e a w eekly (2) 3 tinea weekly RSV 0012856 t Table 17 FLAW OF THE EXPERIUOfTS ON THE BIOLOGICAL EFFECTS OP VINYLIDENE CHLORIDE Experiments BT401 Species at start (weeks) Rats (16) I II III IV V VI Total No. of animals at start Total * (f 9 120 60 60 60 30 30 60 30 30 60 30 30 60 30 30 200 100 100 560 280 200 Treatment Route Bose Inhalation * . 150 ppm 100 ppm * 50 ppm 11 25 ppm * 10 ppm Untreated (controle) - Stopped Ongoing + + + 4 Length (weeks) 21 21 21 21 21 BT402 BT403 Mice (16) (9) Rats (9) I II III IV V VI VII Total I II III IV To tal 120 60 60 60 240 60 200 aoo 100 100 100 200 500 60 30 30 30 120 30 too 400 50 50 50 too 250 60 Inhalation 30 200 ppm 100 ppm 30 30 " 50 ppm 25 ppm 120 25 ppm 30 10 ppm -100 Untreated (control0) 400 50 Ingestion 50 50 100 - 20 mg/Kg in olive oil 10 /Kg in olive oil 5 ic/Kg In olive oil control:olive Oil 250 + 4 4 2 days 2 days 4 days 4 21 4 19 4 21 4 32 4 32 4 32 4 32 BT404 BT4C5 TOTAL Rats (9) I 100 50 50 Ingestion Chinese Monsters (20) I 11 3>*.al 60 yj 95 0.O'-5 30 30 10 17 40 -17 1 .CWJ`1 1 .n:*'1 Inhalation 25 ppm Untreated (controls) - / 4 4 ----- 1 21 13 Weeks start 21 21 21 21 21 21 21 21 21 21 19 21 21 32 3? 32 32 21 13 U RSV 0 0 1 2 8 5 7 (9)" * II III IV Total vv ir.geotioa 100 50 50 a 100 50 50 " 200 100 100 It 500 250 250 -W *6/"6 olive oil 10 Bg/K in olive oil controlsolive oil 32 32 + 32 32 + 32 32 + 32 32 BT404 Rats (9) I 100 50 50 Ingestion ln 4 21 21 BT405 Chinese (2fl) I II Total 60 30 30 Inhalation 25 ppa 16 -35 17 Untreated (controls) 95 4e 47 4 13 1 ' 1J TOTAL 1 2.055 1.028 ] 1.027 | 1 ; / / -------- y / r Table 10 Experiment BT1001 s Treatment: 1 subcutaneous injection of 2 mg of Adriamicine in 1 cc of olive oil* Results i after 38 weeks. GROUPS AND TREATMENT I Adriamicine 2 mg II Control: olive oil Total Sex 9 0* 9 0* 9* animals (sprague-dawley RATS) Corrected Number number Survivors 42 42 35 40 40 30 40 40 40 39 34 30 162 161 129 TUMOURS (D No. * 14 35 12 30 --- 26 WERAGE LASPENCY TIME (we<?ks) First tumour 19 Average 31 25 32 -- -- (1) At the site of injection RSV 0 0 1 2 8 5 8