Document yqrbmKj7kb7QvBzOk547xbJV

MgagAyrg UT!GATON,4tt^j,.- a ^r,,-*..,,-- 2> - -z r* *4 > C i/l -4 C ~i Z CO 13SB,*aGSK^^S3^ I^^wy;>i*rt';ije`ff'Aalypa iu i'j j?;i1! p^frS1 ------------------------------- aaartiijsii",i.i<igixppCT&e.::T . >hiJ5ij;c-. N3 '/v4^ VfUmW ^r---,.u`z^'*urr.,'"u~"znsnjx,1m..<z %rv\--b\vc. tMv^M--v f Dm MU.fill #n IIWTK**V T f frJfwi>V>OSW^WV'i*l>.s'>Ml. m e> so > r.*5^' yo. w-ii-L jeF~F- Vvy/^ WATER_PCB-SD0000063211 MATlSMi MONSANTO IHSLKAWC2 COVERAGE J-'TOATJON CAMCZ?. AS~2 CHSMICA A report Medical C-eparrseno Monsanto CMeaicai Ccrpary St. Louts, Missouri IT IB DUE TO THE OUM.ITT ms an=. s S 3 JJ) S' Prepared sy vtex t. sarreto Marc.-., 136' i STC :520<>81 I WATER_PCB-SD0000063212 WTfcO'H) WAfUlAL MONSANTO UiS USANCE COVERAGE LmGATIQN CAMCSS AND CK3CCA1 ITy.TCT.TiE introduction There la a whole host of theories related to the carcinogenic properties of various specific chemical structures. The latent :f t^is report la to note aam* of the carcinogenic cesspcusaa sad same cf the obvious structural features cannon to compounds with this physiological activity La not the intent to favor aayj one of the present theories covering this subject. The report will he broken down hy structural groupings and is intended to alert research and development personnel to potentially hazardous compounds. A knowledge of chemically induced carcinogenesis is becoming more and more important in the research and development paase cf r.ew product develop ment. Methods cf Test Most cf the cancer-inducticn-oy-cnemical-ccrepcund worx nas seen, and still is done, with nice. These animals are specially bred strains that have exhibited extreme sensitivity >i to tumorcgenic suoatances. The use cf mice in this field has obvious advantages ever other laboratory animals because cf site, cost and space requirements. There are many other animals used in this worn, usually fer specific purposes cr 3w| *XS <>)*: j sn4 ? mr- O 4 hi *2~ nS5 1-5 - -4 * 0 ** W 12" jq - * <4 u(Ai 4 n 55 O9 > 4 C5 -4 8 ro . 4* j STC WATER_PCB-SD0000063213 frcnzcrz? matsw^mowawtoinsubamce ccysuGELmcAnow to fellow up screening worx lone with mice. The worx done aa Bladder carcinogens, for example, utilizes dogs because of the similarity ir. the urinary bladder metabolism of dogs and humans. me compound under teat in most screening worx ia applied ts the exin of tne test animal repeatedly ever a long period of1tine. The site cf application is periodically examined fer evidence of tuner formations and aninala from the teat group are periodically sacrificed fer histopathologlcal examination. There are many other methods of application in this type cf testing, subcutaneous injection, oral adminis tration and tissue implantation are frequently used in screening or follow-up worx where routine screening has indicated some positive response. As in the case in nost laboratory worx, the test procedures and frequently the test animal :f choice is dictated by the compound under test. There are two general types of chemical carcinogens cased on tne response elicited. A primary carcinogen ia a compound that is carcinogenic per se or one that will initiate care ino genesis following exposure. A secondary carcinogen will licit carcinogenic response after undergoing metabolic change. Ir. ctr.er words, the initial compound in this case is r.ct tne carcinogen cut one cf its metabolites ,ia. An i ,I $TS :520*3 **! * ; t ** rc a w' :4i 5 *- Ti m IT 5Wr -4 Ha Wv? -= nr- > r *s4 f L a WATER_PCB-SD0000063214 PROTECTED MATERIAL' WQOSANTO IKSURAi3 OOYERACELTDCAHOt) example of a primary carcinogen la 1 thracene { etnyl , 2-bensan- ana a secondary '.cgen la 2-r.apnthyianir.e (2). (2) in the case of 2~napr.thyia.tine, the carcinogen 1-hydroxy-c.-.apnthyianlne {2-amino-i-napnthci) '.2)* OH ' (3) is a netaboilc product of the parent compound. The compounds that are classed as positive carcinogens in this report are those that have been tested x-ttft positive results using laboratory anHals as well as those that have teen proven in use .as carcinogenic to humans. The text of the report will nentior. the proven human carcinogens in most cases. :t rust be understood that a compound is not necessarily carcinogenic to humans if it is so in laboratory animals. The reverse is also true in some cases. This anomalous behavior -.axes carcinogenic testing for human use a very difficult pro cedure :c interpret. hn 5 S' a 1 -n r> m x 5 w mo 3 il 3% h ww -4 rt: ss; * *H S5 X ro * I 1U j -TC 25204SA WATER_PCB-SD0000063215 ?_ROIsens MATERIAL MONSANTO LVS USANCE COVESAGEifnGAnON I". Chemical Carcinogens A. Non-Cyclle Typea 1. Inorganic Materials mere are a nuaoer of inorganic sueatancea that cauae cancer in humans and laboratory anisala. me following liat indicates one variety of compounds that nave mown mis property m laboratory animal experiments: Ammonium Potassium Selenide Araenie "etal Arsenic Triexide Araemoua Add Beryllium Metal Beryllium carbonate Beryllium Cxide Beryllium Silicate . Cobalt Metal Cobalt Fluoride . Nickel Metal Nickel Carbonyl Sodius Araemte line cxide Zinc Nitrate Zinc Beryllium Silicate Sven 55 hydreonlorit acid will produce stdx tumors aiter repeated applicaticr,. me r.ecnanism of action r.ere would be difficult to predict and would doubtless net be a single mechanism in any eaae. mere are sene interesting bit* of infer ration mat can be drawn iron t.nis work however. m tr.e case of nary r.etais that are carcinogenic, the action taxes place at m.e site cC application. The I tubers Czzzr.zz lr. -:s: :aaes cC slaiI&r type re- STG CJ20V85 3 ** S 3 w> f 3s *3n 5 5-3 5 s5: 3" n r4 3 8: O acn r* ocr* a h r-- a* H8 ;i I L f WATER_PCB-SD0000063216 PROTECTS MATHUAL MONSANTO INS U&AWCE COVHUQEUTXJAnON -5- gardless of the fora of the carcinogen wnen applied. ?or example, .-.ietcel netal powder and nlcicel carbonyl produce similar lung lesions upon inhalation, althougn .ridcel carpony1 Is the more potent of the two. This different s ir. ootency ray indicate that one chemical fora of a carcinogenic aetal .tore readily exerts chlo oncogenic action on a specific tissue than another. The prooiea involved in r.uaan exposure to these inorga nic carcinogens is predominately one of prevention of Inhalation and repeated contact vith the stein, particularly aoraded or otherwise brcteen sycln. Medical evidence on wortcers who handle arsenic re gularly ir. their wonc indicate that arsenic can cause a high incidence of lung cancer ir. wortcers who have teen exposed for nany years. This does not seen that arsenic is specifically a lung cancer agent. It only indicates tr.at the exposure was in the lung througn Inhalation cf excessive arsenic dusts over the years, wortcers m the cnrcnate industry and the nicjeel industry nave snovn 'unusuaiiy high incidence of lung cancer indicating that these setale are carcino genic agents ir. r.umans 'ur.der tr.e proper conditions cf time and sor.centraticr.. STS 15204*6 oe *x wt ># 5 4> z =. n * O3m 2 ?! aw x *r ~-t 5?" S"5 TM4 nfTM;i 5 oc>r-4 s H*>B. . cn ! L & WATER_PCB-SD0000063217 TRorrrrp mathuai. Monsanto insurance coverage uncAnoN -o- 2. irgamc .Son-Cyclic A discussion cf non-cyclio organic carcinogens crust cf necessity discuss the urethsiis. or carbamates, ithyl csroanate \ -) or urethan as it is commonly nown 2.1 a patent oared.-.ogen as well as a earcir.o- ~ ru\. G, ' N- SHo ,H) >tapis substance used in t.-.e treatment cf leuxemia, a serious cancerous condition cf the blood forming organs. One can only speculate as to the mechanism wntreby ethyl careamate or any of its derivatives of lesser activity initiate the production cf lung tuners, the similarly high activity of ethyl carbamate per se suggests that the intact .taiecule rather than a r.eta oolite precipitates the oncogenic process. It is imprcoaoie that the degradation cf ethyl-K-methyloarbanate :;) for example, differs in general from 3 ;s) that of the nor.aiicyiatea ethyl oaroaaate. The forme should have exhibited a peter.sy comparable : o the latter if the cr.coger.ic process is initiated by a STS Z3204* 7 4 s*s a m3 --> nS 5 2>f w --Ipr> g ** m 8sJ 8w1r-r H -O4 vWi -s4 nr* 5. Oa J 4 r--H 2*2 ' Cn ro I 5 !f i* i i WATER_PCB-SD0000063218 P9.CTSCTW MAtSUAt MONSANTO INSURANCE COVERAGE LITiCATJON ostabollts ccws to the ewe compounds. If one unati z?i*t if ethyl caroamate exerts its effect as an lattet ooleeule, it follow* that the oncogenic action of an alkyl urethan nay t>e due either to the compounds as such cr to urethan resulting from dealkylation. The latter possibility would appear to be supported by the unexpectedly large nuaoer of lung tumors tr. & group of aloe that has been injected with ethyl-N- isoprepyi carbamate (5). PH* C - H TH, 3H - (6) Had the relatively high activity of this compound, which sight have been expected to be of the low order of activity of other r.ono-ailorl derivatives, been dependent upon the presence cf the allgrl isopropyl group, the dlisoprcpyl compound might have ceen expected to elicit more tumors than were coserved. The data resulting from the use of three dlurethane tend to support the nypothesis that the cneogeme action of alkylated urethana occurs, at least lr. part, as a result cf preliminary dealkylation cf the mole cule to ethyl oarcanace. Jne may regard a diurethan e.g. .-.ethylene dluretr.an as a suestituted caroe- tnsxy etr.yi carbamate. s' STS 2520AM S4 4 Hh "8s O -5* *n" -a nm cz a * z*ow sw i" jnr; ? -O* iirnt. 4 n zw r* os -4 X ho / J 4 WATER_PCB-SD0000063219 PROTECTED MATERIAL MONSANTO mUSANCE CCYSUCE UnCATJOfc! ' -o/ Of the three compounds tested, ethylidene diuretnan (8) exhibited the nigr.est tumor eliciting activity. 0~HeQ H JDC-^Kc SC - s' - - K - ' 3 CH, 0 (8) mis compound disassociates freely ir. warm aqueous solvents to acetaidenyce ar.d uretnan. It is prooaoie that it behaves similarly ir. the mice and that the large mean number of lung tumors were initiated by the liberated 'uretnan. Methylene diurethan was somewhat more stable and produced somewhat fewer tumors on the average, rthylene diurethan gave r.o evidence of disassociation into the intermediates from which it was prepared and exhibited an activity sore comparable with those possessed by the nono- a_lkylated urethans. There are ctner r.cn-cycli: crgamics that nave snown carcinogenic activity in laboratory animals. Aee- cylchciene (.9) is an example. This substance is 1 CE, l - CCH.Cl-UlHCK, " (9) notsally present is. tne r.`jsin oody and takes part is. very ispsrtaat reecasolie reactions, Careen terracnlcride tic) r.as caused Clver* vrsors ir. laboratory *.en asjtlr.itterec orally. C1 i 2 - c nlc r e e er.y. STS 2520089 I *s4 r. H ffl j' nsm *3, -5n3 nn ~x wx -4 >O owm gm^ g VI w rm j U) OW -4 n " 5. >H rs -4 * I fS3 4 'A ,I L WATER_PCB-SD0000063220 ?RUia7LS MATBUAL- WOW5A.NTO INSURAi><2 COVERA UTJGAHON 3 ) aaine hydrochloride (11) ana Beta, seta priae-dich- CiUCH-CL , HN 4" -SCI ; " CH^CK^C- '11! lorcdietr.yl sulfide 112J as well as cetnyi tla (beta :^ *25 onleroetnyi; asir.eilp) and it: h.ydroonlcride nave ^ v.t, -n ^tr r\j -- CH C X Z " *2 "'2* (i3) caused luces cusors m laboratory aniaals. These coa- pour.ds are generally classed as srustards or nitrogen .custards ir. the case cf the amne compounds. They have also oeen used for control of certain cancerous conditions. As in the case of the urechars and Ionia in; radiation, these cancer therapeutic agents are often also carcinogens ar.c can initiate carcinogenesis in certain instances. Thicacecasside ill) and thiourea ,15) have produced liver :x_ - : - s>:_ ii', ; - : - 'V.2 vers --,, ,dCd*<L*cr'-y' d.s*, 15; i*ccr*ox STG O n *s4 *4? ^ V) S 3 so-i w 2nr 0mx 5-5 a5 *4 >CmJ 1 S55 2"!; :< 3$ -x4 Or. 5. o ?r *x4 0) S; i\- 1ii 1u WATER_PCB-SD0000063221 ?R0TBCT3 MATERIAL' MOWSAKTOLNSUSANCE COmuOEUTSGAnOf. :r isopropanoi (IS) by innalaticn cf 2000 ppa tjls ch; \hc - :h / . ch, ;:S) produced lung cu-tcrs ir. sensitive laboratory anlrnls. mere r.as seen ir. general cco little nusan experience -ccr. tr.ese nor,-cyclic ccrspcuncs co evaluate tr.em as ^n cancer agents. In t.ne case of ccapounds used in tr.e treatment of cancer, cr.e dosage* adalsiscered were generally higher than would be expected in tie usual industrial process. The carelncgenlc activity exnibited by isopropar.ol is difficult to explain. "3 This is eit.ter a case of a ccspound t.'tat is Just not i p.'jAn carcinogen or it is a ease of exposure to con centrations cr.at are not experienced industrially. In eit.ter case, cb.is eccpcuna r.as never snown r.usian response corresponding co tr.e ar.inai response alt.toug; it r.as ceen used industrially and =edicinail7 in greai ruanricies for many years, cclltcucusar arnac*c Cvrcpcunts I mis group cf eexpounds r.a* ceen studied ever since coal-car cancer -as descrited r.cre cr.an a century ago. mere is r.cre data availatie cn cexpcur.ds cf cr.is cype cr.an any ccr.er group, m.is sass cf litera ture raxes it pcssiole cc discuss scructurai cnecnss sTS :sao*t,v n x iw *n x c3 *3r*J. mnn >rz" "4 C/3 M ' o ro i t 4 WATER_PCB-SD0000063222 PROTECTED MATERIAL MONSANTO iiLSURANCX COVERAGE UnGATJON cf carcinogenesis along wit.". & discussion cf this group as a wnole. Human experience with compounds of `.Ms type has shown that lr. certain circumstances they are nuraan carcinogens. The scrotal cancers In chimney sweeps lr. Europe as well as c!-.e coax tar cancers were oDVieusly causes Py polynuclear aromatics adsoroc. :n chimney soot and contained lr. coal tars. In recent years, trte .`lad Incident of serosal cancer in wax press sen lr. petroleum refineries was traced to polynuclear aromatic contaminates found lr. the feed stocks as well as tie supernatant licuors from the wax presses. These compounds have exniiited some strange charac teristics which influence the seriousness cf the taxard associated with handling them. Their aoillty to tightly adacrc to certain careen ,soot! particles ".as ur.dcu&tediy limited the carcinogenic r.aaard in nany cases cf exposure to the skin. In these cases tne carcinogen is so tightly adsoroed that it will not desoro and rsaasore to the human skin. so haaard exists unless the soot is held in intimate contact with the skit, ever long periods of time. m the ether r^nd, this is not true m t.-.e case cf dust exposure -nere innalatior. cf t.-.e career, particle as well as t.-.e STS 152Q49Z OB HX ** H 3 H' 5 =. *In O*--B *Ho rm awe m4 * >X m -X rHr B * W 8 "~ 52 S ' 37). ho *g S> *H rx ro - A L WATER_PCB-SD0000063223 fzvtzctzs mattdual >ksanto lksisa.no; ccvbuoe unoAnon it- adsorced carcinogen will place the carcinogen in contact with the lung tisaue and remain in contact Ter long periods of time, experience has sr.own that good personal hygiene and proper respiratory protection can centre! hazards of this type. Care rust oe tauten mere these carcon particles are in contact 'ith organic solvents i including lubricating ells and "easesi that these solvents do not dissolve the carc-incgen off the soot. This of course could result in the solvent solution becoming a carcinogen.!: hazard. Some general information oor.cerr.ing the carcinogenicity of polynuclear aromatics is necessary to understand same cf the structural relationship connected vrith active carcinogens as well as certain theories concerning carcinogenesis, "or example, 1,2-benzartr.raoene .1") the parent compound of many carcinogen:, io imi*'* U 4' 5sS O 3r S o w s 1r - h X*ci 3*- iS" 2"5 :* 3 $ -i o 3w P*- >M -s - -4 S C/5 S' fO A i ST6 1520193 WATER_PCB-SD0000063224 PKOTECTES MATERIAL i lONSANTD INSURANCE COVERAGE LmCATiO.N t-13- t.n i , 2-bensantftraeene derivatives. This compound Mi & pentane ring fused ts the p, IS eancons and a aatnyl group cn the 6th caroon (or tne 20th canoon wnen naming as a cnaiantnrenei. If tne raetnyl group sn t.te cth careen is removed, tne resulting compound, :nolant.nrene -,15) is^ainoss as potent as rjstr.ylcho-v' \ lantftrene, snowing tr.at t.tis setr.yl group on tne cth position contributes very little to the carcinogenicity cf this compound. If the pentane ring is opened, the resulting compound is 5, lc-di.tetr.yl 1,2-benzanthracene 20). This compound isp^lsa aeeut as potent as the 20) paren r.etr.ylcneiantnrene. f the setnyl group is removed from tr.e ; positicr. saving 10-methyl 1,2benzanthracene (21) thep^enp1 und still retains almost 21) cne aeries if impounds antnrene in is tr.e carcinogenicity 520*9** SIS 3^ X ^ 3 H|1 5fn -33 3nn> 1*"i x * Ti W ; g v> twS i -a4 w -=n nr 9* > *4 r-- x 4x (/> iU f WATER_PCB-SD0000063225 PXOTBCTS; ^TIXUt-!40NSA>TOWSL3UWCE CCYSUGE UTiCATiCU b cf this compound is associated wit.". t.".e ID supstituted retnyi group, This r.etnyl group is attaened to wn&t is Known as a nuclear r.eso carson. There is another nuclear r.eso carson in the 1,2-benzanthracene structure. This carson is ir. tr.e 9 position and 9-ethyi 1,2-ben:anthracene '22! is arrest as potent as the 13-methyl "U- \ 1 oooerately potent'carcinogen :/ itself which r\ay tenc :o explain w.-.y i;-dimethyl 1,2-benzanthracene is some nat r.ore potent than IC-metnyl 1,2-benzanthracene. If tetr.yi susatitution to the reso carsons is related to tarcinoger.is potency, then a compound with both these :arsons substituted, such as 9,13-dir.etnyl 1,2-benzan- tnracene should be r.crt-^otent than c.he mono 3m. *s* **> *n j W Hh g V> mC 3S -x* nr- 71 5, os >r *x4 ro STS ZiV**** 4 WATER_PCB-SD0000063226 PROTECTS AurEJUAt- WCNSANTQ INSURANCE COViSACZUIlGAIJOtil -15- 3 csarpound is second only to the metnylcholanthrtne is potency. This discussion leads to soae structural indication chat seso substitution imparts carcinogenicity to compounds of .the 1,2-benzanthrecene type. This is further tome cut ty tne face that u,9-diaethyl 5,5tenztnicpner.antnrene '.25! is as potent as 9,13-dimetnyi M. z m: Hw 5 * fi' -or asi z> W -2 r o H *nw 8" - 58 " 3" r 0 V) h a s r* n 5, P *4 --rH* sp8 \ 3 1,2-benzanthracene. The benxtftiophenantftrene derivative is similar in structure to the tenzanthrscene but has a thiopentene ring fused to the nucleus where the benzan thracene has a senzene ring in the same position. is a natter cf interest, it should be .noted that 9,12diretnyl 1,2-benzanthracene is sore potent fcr stdr, cancer t.nan is setnyl-cholanthrene cut r.ethylchelanthrene is more potent in the case cf connective tissue cancer 'sarcomai. Active carcinogens snow no tendency to enter into additio reaction cut they snow a rsaarjcaole susceptibility to substitution reactions and surpass all other Known aromatic .oydrccsrccns m this special chemical reactivity Appendix Figures 2 and 21!. 2t will be noticed alter STS 2520496 roi* i L WATER_PCB-SD0000063227 PROTECTED MAT2UAL MONSANTO INSURANT COVERAGE L/nCATON -16studying Figures ; me 1Z that 2, l-benzpyrene (251 (26) and .rethyl-cnolantnrene ilS), both potent carcinogens, give very excellent yields upon addition cl certain reagents, me suostituticr. noted here are all in one 5 or =eso position or. tr.e cenrpyrene nucleus (.Figure A relationsnip to neso sucstitutior. causing great potency in benzpyrene should not be overlooked. In 2,--benzpyrene, the substitution reactions were througn the r.eciear r.eso carbon. In the 1,^-benzan thracenes,. (.tetbylcnolanthrene - Figure 22) the sub stitution is to a sethyl group attacned to these reso tarcons. Spontaneous nussan cancer nay ce causec by tr.e operatic.-, cl encogenlc carcinogens derived frea steroles vFigure] The initiation cl taroir.ogenesis b7 a hydrocarbon ray be asaociated with inter action with, a ceil constituent by suostituticr. at a neso position cr in an alkyl group located at suer, a position. in interaction with a disc Tide linkage cl a protein r.as seen suggested as a possibility and is supported by the ccserved reaction ST 2320197 a-i hx *T; 3 5 Ml "OH *"* 2a Rn 5s *x re w* sw 8M 5 S" 3"5 ^38 hn 2 r* o *' r-- -t x8 03 d/ Q PO * 1u ______ 1 UQ WATER_PCB-SD0000063228 ?T0TECZ3 MATERIAL MONSANTO INSURANCE CCVRA L/nCAnOh' with thiocyanogen (Figure ITT). The Bile acido and cholesterol Belong to the general group of steroid substances which include r.araones secreted by the gonads and by the adrenal cortex. The fact that 3 steroids present m the organism (Figure ITT) have been transformed by eneaieal processing into an active carcinogenic r.ydrocaroon \metnylcholinthrene i suggests the possibility that comparable processes ray occur in the cody and that a stercie, bile acid, sex narmcne, cr adrenal cortical hormone may be degraded by a process of abnormal metabolism to a substance capable of inducing cancer. The electron density theory' sf carcinogenesis b7 hydrocarbons is an extremely helpful bit of information in the evaluation, of compounds ef this type for possible carcinogenic activity. If one considers li-dimetnyi 1,2-benzantnracene '2''. 9,IC-dimetnyl 1,2,7,E-dibenianthracene (27) and 9,1 c- Om *s4 * jSj 5 i S' OHn CN5 > X IS'" 3"5 -4 - W 0 Vt -sn nf^ 8* *r- <x*4. 3* ro 'A STS :S20V98 WATER_PCB-SD0000063229 PROTECTS MATESiAi-MONSANTO DGUiU^ COVERAGE UTJCAriOa -10fact that the latter cf these three ccapounds is an inactive material and the first two are very active saterials. would indicate that the first two eospounds contain scree key iinicage. If these three ccspounds are studied in the light cf their structural characteristics and the fact that 1,2,2,--ditenrpnenantnrere i 29) is an (29) active carcinogen, 3-metr.yi 1,2,2^--ditenxphenanthrene (30) and 10-r.cthyi l.i.J^-diSentdhenanchrer.e i'2i) are (20) tsth inactive materials, it teccr.es apparent that the pner.anonrene dsucie tend is cf structural significance STC 1320*99 3i *s4 *n*< jw j Saw O3,, |p i 5a - -t ; $"I 5 5 s' S"; r* 3 S -4 f ^I -4 : < </> S' ro * ii LC WATER_PCB-SD0000063230 protected material monsahto lssusanoe ccvBUGEUTiGAnoN -19- ir. this prsoiea (figure r.'). The asterisk lr. figure r.' shows the pnenanthrene double bonds. All of the active carcinogens in the above group contain unsuostituted pnenanthrene double bonds. :ne cf these compounds contains no pnenanthrene cone ana it is an inactive compound, and two of this group contain a metr.yl substituted pnenanthrene ccucle tend ana they are also inactive materials, from this line cf reasoning, cne would hypothesise that a_n unsucstituted phenanthrene couble tend is necessary to impart carcinogenicity tc these poly nuclear aromatic compounds. However, 1,2-bencan- thracene (17! is an excepticn to this rule since this compound contains an unsubstituted phenanthrene double send but snows no carcinogenic activity. Also, if a methyl group is substituted in the l or ** position in 1,2-dentartr.racene, it dees inpart some carcino genicity tc the compound wru.cn contradicts tne theory previously postulated. ' It has ceen proposed thet the electron density at the pnenanthrene double tend in t.he centantr.racene molecule .ruse be aDove a critical limit for carcino genic potentiality cc appear. The order cf electron tensity m different propounds approximately corresponds with. ao would be expected frer. tne order of biological 3T5 :S2050Q o * --. e s r -t si H` "I" aw -or a pi x y rn z o5 w w IS5 gWr ow -4 n os c> M r- sy8 I L WATER_PCB-SD0000063231 PROTECTED MATTOAL MO6SANT0 INSURANCE COVERAGE LfHOAHON -20- potency cf a tenet or carcinogens. The aeterslns.ti.cn ;T the electron densities in tnis theory is very eatspiicatea cathnatically. This theory does, however, postulate a .tecnanisa that has neither teen proven nor dlsproven. The activity or the carcinogen, according to the theory, i: sue to the eiectror. affinity cf its excited state facilitating a quanto! changed ir. neighboring nolecules. Recently this theory has teen supported :y wont or. quantus treatcent which percits the calculatlcr, or the density cf an electron for a given strue rare for wnisn it is ciaiced a relationship can te fcrsulated between carcinogenicity and the electronic density ir. the region K (first shell, principal quantur. so. r. : i;. The density tnresnold oelow v.'nich a susstance ceases to be carcinogenic is '..232 *. :f or.e considers the pr.enantnrene structure, it is reasonably easy to see that this polynuclear resonating r.oieeule is polar cr is strained. This strain creates an electron deficiency through certain positions and consequently causes an electron excess in ctner poaiticr.s. This excess is created by the electron affinity of this polarised group, Tr. the tonal resonant state, electrons tend to be drawn s oward the pner.antnrene ooutle oor.d wr.icn would snow ) STG 2520501 *4 ** x ** ^ fi n o 3^ -- -d nn rx I'-5 o *- n 8"5jn?r" -4 *o4 Wcn -4 n xm rJ o > *4 >4 X Hj CO LU WATER_PCB-SD0000063232 fttCrr&CTED MAfSUAL* MONSANTO COVERAGE L/HGATION -21- i & hig.Ur electron density. The K level electrons ' from this bond area, according to the theory, would then initiate certain quantol changes in the K ieve.' of an adjacent electric structure cr atoas wnlth would in some unexplained .tanner initiate carcinogenesis. The electron censity theory can oe expanded to cover certain non-polynuciear structures cy the same elec tronic considerations, "or example, consider --dinetr.y amincstilbene .22). In this compound it would be - -> t i a e **. m s mi 4 S *> 5*M a9 3M m 3? 5 l M 5.' r *4 >\ qm S'8- FJ os > n? H> </3 necessary for the molecule to ce capable cf assuming a quincnide disposition with an electron donating group ir. one ring, conferring a high degree cf negati-e polarity in t.-.e ctr.er, and the outstanding feature being the necessity for ur.sucstituted hydrogen atoms in the ethylene cridge and in the para prime position. Such a system would appear not mereiy to contain a structure in the ethylene cridge wnidh is analogous with the pnenanthrene double bend in the eyelid hydro carbons, but to possess electronic characteristics which are produced or. condensed systems cf benzene rings cy a ratr.er different means. In ctr.er words, the influence cf an electronegative suestituent in STS 1320502 WATER_PCB-SD0000063233 ^OTZCTES IAATBUM, MOttSAXTO IKS USANCE COVERAGE LfnGATON Ci" the para position or. one ring in u-dlaetnylaatnostlibene influences one resonant characteristics of the molecule such that the ethylene bridge between the benzene nuclei snows an electron excess similar to the electron excess exhibited around the phenantrtrene doucle bond, "our-dime thy iaainoatlibene is a very active circinsgen. lh certain theories, the nydrocarson itself is not a carcinogenic agent cut one of the metabolites or the energy release during the transformation from the parent to the metabolite is the causative agen of cancer 'figure V'. In the case of bencpyrene {25) the metabolites ctsec-ved by their selective fluorescence have been postulated as the carcinogenic agent from benzpyrene itself, "igure V shows the r.etaceli: reactions cf benzpyrene It can ce noticed that the ultimate metabolite from this system :: -benzpyrene! ,'23'.' The intermediate products cf this metacoiic system are alkylated alcs.no According tc the t.necry, either one cf the metabolites ST& 2520303 0 4 > II")' j3 j Sam a3m * c ** 38 5 1w3 r *4 ? sw 8" - 58 * gnr >4 I S! V 4 ' ,I UI J WATER_PCB-SD0000063234 PROTECTS MATERIAL MONSANTO INSURANCE COYERACE LTDGAHON 23* t> or one energy necessary for one transition frna the parent to the metabolite is the carcinogenic agent. In Appendix 3 of this report there is an extensive list of proven (in laboratory animals) polynuclear aromatic carcinogens. This list is not necessarily complete cut gives an idea of the structures involved. Also in Appendix A there are two tables (numeered 1 and 2} showing relative potency of many of these compounds in adtual comparative laboratory tests. Tables 2 and tt in this appendix show some reference to tumor induction time (latent period) and the single injection induction time. Bladder Tumors and Aromatic Amine Carcinogens There are several materials that cause bladder tumors ir. different animals. Some will cause tumors in rats and mice wnile otr.ers will cause tumors in man and dogs and not in rats and mice. It is tr.erefere rat.-.er difficult to postulate a t.-.eory covering bladder carcinogenicity in general. hcsc experimental evidence indicates that tladder carcinogens are clcseiy related to materials carried in the urine, huer. experimental data point to this fact. In cne case an experi ment was conducted whereoy pieces cf rat bladder were grafted into cne -Ivors cf corner rats wnlch were m turn fed with a I STS 152050* 1 I 01 X ** -a An cx 2> m r 8w 3 S r* 3 -5n4 ro * 1 WATER_PCB-SD0000063235 PROTECTS! MATERIAL MONSANTO INSURANCE COVERAGE LTOGATiOtj -?Liiet cf rice, f1cur, and 2cotciuene (3*) (a potent iiadder Hi C (3") carcinogen ir. Rise.'. A high proportion of intact didders in cn.ese experimental ~ - is snowed tumor fcrmaticn wnlle in no case would t.ne claioer tissue c_n t.ne liver exniiit any evidence of tutor:. 3eta-napntr.yiar.ine \ 2) has seen a inspected carom.genic materia- for years. Attempt! to produce tutart in experimental animals failed until an atter.pt was race using acgi. If cne reasoned from these facts t.-.at dogs and Humans are inherently susceptible to this material wnereas doe, raotits, ant rats are not, tr.en it would naturally follow t.nat ssr.e specific reaction taJcee place differently in nutans and dogs than in tt.-.er experimental animals; :.tis is an exoerir.ental fact. 3eta-napr.thyla.tine lives a retaocli: end product of 2-a.tir.o-i ,-naphtha! ;2) sulfate of) wnereas tns ct.-.er species secrete S-acecylaninc c-nydroxynapnthaiene t 23). Vt -W-v-v.-.-j HO w The casis cf one of the cr.eeries cf Pladder carcinogenicity is t.-.at an aromatic amine ccr.oeur.d, prosaBiy polynuclear, -use :e acle to ce r.ycrcxy.ateo l.n t.ne position crt.no to t.ne STS 2520505 4 W a nn -ie 'x> ** -X r >rs o * w 2h fS3 A 1u CD WATER_PCB-SD0000063236 forcer MATERIAL MONSAKTO UiSURAJ< COVESACSUTJCATKRi ) amine group, tf-ere is no proof Tor :!Us tr.eory except tr.e musuai Tact tnat beta-napntr.yiimine causes biadder tumors in humana and dogs wnieh excrete tr.ia metabolite and does not cause biadder tutors in tr.ese species tr.at do not excrete it. ?r.is same phenomenon r.slds Tor tn.e carcinogen u-aminooipnenyi or para-aminooipnenyi or xenyiamine ) (26). According to tne present stato of tr.e art, severai. aromati: amine: are considered titan oiaider carcinogens. me first of these is teta-napr.tnyiar.ine (or 2-napnt.tyiamlne} (2). 3enzidir.e i or - . - ' diaainooipnenyi) (37) is also a proven O *4 **. * S "V 4 H* O4 58 5 ^n r - 5 Wm a* - ? " jnr h o Utn 4 n sn rj- OB > 4 rx M -4 S N5 ; ') i i i is also a proven .-.tsar carcinogen, it is interesting to note tt,at aurariine right be r.ctatsiitiily converted to ,n,.v-tetra-etnyitensidine -.33) 'ricn is an K-alVcyiated teniidine that i STS I3Z0506 > i WATER_PCB-SD0000063237 PHVTZt nr MATERIAL M0.N3ANT0 1NSURAKZ COYESAGE UT5GATJON -26- ,ui ilre&ar teen proven carcinogenic in laboratory animus. :t is necessary here to point out that soaething In the .oagenta (-0) process causes r.unan iiactier tuners. It is HsN</ ^ Ti C a {'' SN Sn2 ^ :-o) s>w. 0 " ?2-2--'/ lr.tertotir.5 to note or.at or.e :ase ois '.--a.7U.no ; .otonyipnenylre or.one '1) is a dinet.nyi K^N^/ \\-c---/ ("D derivative cf nethyisns cianiiir.e cr bis (1-aainopnenyi rethane -2).wnioh is a proven carcinogen In rats according x\-c_. ' \ NX., ("2) :c reoono Conran studies. "any derivatives r.ave oeen proven oo oe carcinogenic by lasoratcry tests . The compound 2,2'-linechyl---tnanoDipherTyi '3) ~i hlgh.ly carcinogenic in rats. ether ienvatlYes cf ai -a 5 %m M Ml or WX z-- >WZ s H >mn 5w ss" gn r -4 ho -4 n sr os > *4 r-- s> ro * -j `i St6 2520507 L WATER_PCB-SD0000063238 PROTECT^ MATSUA1 MONSANTO LNSURANOE COVERAGE LmCATTON J until thorough laboratory studies ind.cate otherwise. This would include halogen derivatives, nethcny derivatives and soth C and K alVylated derivatives. There are a riustoer of cen.tidir.s ;~) derivatives that are <r,cwn to be carcinogen: >r. -- * ir.o ;;r.e suspected. in nunan cancer involvement. There are crtr.c-1o-lllr.e , ~ and did.olcrocenridine i"5). </ V/ '-2 (*J3) 7..S Ine ;-5) has rover been proven to be ..-JUv -J* *. * 5S // v/ ' VTH (16) carcinogenic although great dre mould be exercised In Its .tan'*ling cee&use of It* close structural sisilarity to the parent bsntidlr.e. . There are some amine cor.pcurds, closely resending Known carem.oger.s, tr.at .-rust :e watered carefully although no clear evidence is available wrecrer tr.ese particular corpcurds are carcinogenic ::: se. This it particularly true cf alpha- STS 1520508 0 4 *"*. 11 F5 s n Q3^ iSi >w2 r oo -* w >ow g5 jnr I *j w ow -4 n sn r- os * H 0 ro 4^ L WATER_PCB-SD0000063239 pnoT&zrrzz material Monsanto insurance coverage litigation napnthyl -28- ;e i (-7) and diphenyl&rlne (-8). (*7) I.-. case zC alpr.a-napnshyia.tine, it It always contar.ir.ased -ish t.-.e carcinogen- :sta isoner. Biphenyiasine cn the ether .-.ana is usually senca.dinaced with --asinoaiphenyl. It is interesting to note that lens tern dog worh on I*-aminodiphsny lanine {-a) does not indicate that it is carcinogenic. It Tall: t.-.e let or the Medical leparTner.s to answer the very dimtu-t question zC wnat it cr is not carcinogenic. The lepar-tr.erc' s answer in air as t all oases rust be baaed cn .taay ratters. lose cC these factors ire: A) is it similar ih stricture to Vnovn carcinogens? B) His it ever o-een tested Tor carcinogenic activity? IT sc. -nat were tr.e results and the conditions, of test? ihir.als testes, concentrations, tins, sethod cf alninis ST6 1520509 Ow HS ** 4 X- >mX rh w awm r12" jnr i -x* nr* n 5. oa *4 r-* x -*< z 0) s ro A WATER_PCB-SD0000063240 PROTECTED MATKUAt WONSAKTO INSURANCE COVERAGE LmGAtTON I -* -29- (c) Is the compound presently being sanufactured or used by ary other ccapany or research group? ir so, wno and wnere? In writ's physical forts will the cctrpound be during handling? 'Solid, gaseous, liquid). *hen one Medical Separosens suggests carcinogenic testing, is will usually require iron two so live years so obtain ary ir.terpresasie cast. even wnen ouch seats are perfcmea using sr.e best ccehricjes kt.own today, sr.e resulting data are often not conclusive. frequently we crust nay.e tegpcrary educated guesses. Ve hope, r.ovever, Shat eventual conclusions concerning the advisability or inadvisability of rzJELng or handling a specif!: class of ccspcurds reflects an appreciation )! for ail available facts art: infcrr-ation and the necessity for Urination of any significant ristc cf exposure so Monsanto eapicyes. O-n *s4 ^ Ssn O3e nSi >MZ ''S 5w ss5 24 3<W/> -x4 nroa ?H r---t s5S* c/> d o ro ttJjSSteh St 6 520510 ;I J 4 WATER_PCB-SD0000063241 PROTECTS? KATEUAL MONSANTO DiSJ-RAMX COYBWOEUTJGATTON l AFPEHLX Substitution Reactions of 2,- Senipxrene Figure : Figure V Table i. Table 2. Ti ie l Table "henanonrene Send and yeso Carbon Compounds P. V Metacoli: Reactions cr Sencpyrer.e - ?. VI Carcinogenic Compounds Arranged in Depending Order of Potency m Inducing epithelial Greers by SV.in Painting or StocK Pice - . ?. .i'll Relative Carcinogenic Potency or Hydrocarbons Cor one SJcin, Subcutaneous Tissue and Lungs of Mice - ?. VI" Approximate Clascificaticn cf Eydrocsrecns According to Latent Period of Induction of Sarcomas in A Strain Mice - ?. HI Lndueticn of Subcutaneous Trocrs in C-,H hiee ith Single Subcutaneous Injection ef'Carcino- ger.ic Kydrccarccns - P, ,v, a *4 e x e Ssn 03e HfiS 1-X r H >o 2 >> in IS w jnr - ) HC vVi! -t n =r -> 5, o ?H rx I Lit I STS 2520511 L WATER_PCB-SD0000063242 P^OTECTET MATERIAL MONSANTO QiSURANCZ COYOAGELT73GATTON ?ZZ'C?S : Substitution P.tactlsna of Sentryrgne 4 a * snN o3 i2 o ow om sigw~ 5w5 -4 ^0 VW) -4 n S o2 c* w r x> HB 0) S; ro H \ o-c "n-3 A 5 Acetcxy-3, - 'ztr.z^y Ii i ) L STS ZiZOiiZ WATER_PCB-SD0000063243 PROTECTS MATCUAL . MONSANTO DURANCE CCyERACLfnGAnOtt ?I*V?.E II u a-ntr.rere *r^` 3 A:e:cxy-cv ocyajso ere cr.y 0H 1 X T HH n sn o-r> n4"m r--s* x> 1 vH* tn X*r> iS" 5 -4 wi c v> hn nj c >h <4 x C/3 ro -TS C 52 05 13 / WATER_PCB-SD0000063244 TROTZCTZ: MATERIA!. MONSANTO INSURANCE C3VZ2UCE UwOAHON ') Carcir.csens derived P?r", ^;eroIs "*5 ~-a i rescx7 -- 5* \ \ \ M.etn7 ia^tnrene o 4 ** ^ 5 ^. ^ W Hn*n 3 3 >! 3> " " 335 I'- X "*33 Hw sW SS " 3" 3 ^3S -=n) rrw>> 1 oa > ti PO I ) l1l I - ` : CS20J14 i WATER_PCB-SD0000063245 r PKCTZ/TTSD MATERIAL MONSANTO LN5 URANCZ CO YT&AGc. UTJGATTON pnenan Bond in a V*so :ar"-rr! C s 3 - " ^ Z^ 4 ** n Jit m 3 3 " S5 >MX rH > 3"" "i?1'' awz -j n ri ^ ox > * r-- s> ha K3 * 1 liter .an -.e i tr.yl-1,2,2, - difeentcnersn rene ,Inactivej :ts zizzm L WATER_PCB-SD0000063246 protects: matsual- Monsanto ixsusA>>CE coverage t/TJGAnoH' 1 weta.tcl >X/ "V" X. 3n a *n -4 W -4' nO3} afHoc nn nS5 M J> H< * PO A ,I II I STS 2520516 WATER_PCB-SD0000063247 i i PT.tJTZCT WATEUAC. * MONSANTO INSURANCE COVERAGE LTHGATiCN v*' 'S' UU(?0 muw o , f* i r -? ..* ro n r ** C' f> i ** 5 O'. 6 ~ r r> t- v * o 3 3* ?} 2 0 1n n --* o 3>v<<CiN3 I3i>-< * C3 *- : vo *C w 3 '.o1n3 3 '1*1 r* r* < <-* O 33V. :< ;nyw -a 'i C' 3O * f* 3 3 N 3 v< n f C* 1 ? *3 r* -- ' n i 1 w 3 -- 3^*Or*Ct* 933 o2' i1v*V r<ar no* >i -'**<~ lu a i 1 *< r tS - o (% O -V **3 <r 3 n 9s N rv cr N N *- w" 3 -5 <"> r 3 V* o 3 9 33 N iV -1 1 1 ' O M - 1 3 I on ' cr n o 3^ N3 '3 O N 3 3 X 3 r* ^ ^ ^ v^i v/ --*; V** s'o-'^C'*''LCx3J-WfOrV:U--J cro m3* <C" MV -* -J MW-vuDw'inou <r- o im -- *3 53 w> - I 0 f O < --' i *<1 r* r* u *+ i *i 339 C. CT C3 ~g ^o X * =3 n m -) 2 no 2TC C520517 01 *4 1 j Ifl j Sxn o3 CaJ -nW ---X 3n -* M r3 H )I CO ms o jo WATER_PCB-SD0000063248 (V t }*> WQ^ANTOC^USUMZ CCV'S^ACE UTKIATK^' i 5 7 3** **9> OW 3 r*> ^ o rj \jy C' C C\ ! f * ^ c. ^ 7a? 7) 71 ' 3 33 o o - vr -- - < a i -3 3 30 3. 3. 7* 7? *C Or* 9rr *O- 3ft 30 C! ci i r* \ zz 2 -<1 i 2 5S OM r 5; 58 52 O r ca VI -? 2 gSj rn k ' 3 ig r S < IIT 2 li -i 5 ?f > 3? H 2 .w `J ZM nu . '* si m C4 J2 -1 -c C<o---?-. ocr3 C ** 3O STC 2520518 O-1S* T h 5 j' in * cx> 4** * -anorx x> -2 r -t > j 3 "w r - is 3n "3 >r: H1 < -- -- </) H O - N5 A SV--*. . LL j *w 1 *a i j pw %aa 1 * * WATER_PCB-SD0000063249 I =*aTtC7S3 MATERIAL MONSANTO INSURANCE COVERAGE UTJGATSON 1 TABLE HO. i XSSZTZZXZZZS C? KYTE0CAR30HS ACCORDING TO LATiT-rr ?SRIC3 P IHOL'CTIOH C? SARCOMAS LS A STRATH MICE Iz.i .i-er.t perici Moderate latent person HA&h latent penoa i 1,2,5/ 6-Gibertint.tracene 3, i-&enrpnenantri.,ene ::-va*.r.v::r. = :.r.re^ ?-Met.v/l -1,2-ten2ar.cr.racene S-Hetnyl-i# 2-benrantnracene ; , 12 -21-*zr.y 1 -1.25en^n:r.racene 5-Mecr.yi - ;, 2-fccn::ancrra- p-Motftoxy-i, 2-benzan- cene `.nracene ? i j> 0 -DIjzc ry l"-i4L-bcr. z- 2 0 - Z t.*. y 1 ss 1 an tr.rene ancr.racere lO-Ketnyi-l, 2-benza.-.tnraoere 2-Metr.yiterzp.-.e r.an t rr e r. e 3 \ 2 ". m *4* 5sn Sw~ flSS >mX o * m 8"- SS" 2wr -4 n sr n jj os *M -x --9 -4 X CO IWIII'IIB o ro ii ) i ' i i ST6 1320519 i' WATER_PCB-SD0000063250 pp.orzcrzz j^rm>u-^MO^>^TOLS5LSANCZ ccysucs lTwCatton 1 in u f i. i * f TABLE NO. ? lEVBOLTANEC'JS 7VM0P.S I?) C^H JdCE VT7H SINGLE SL'SCL'TAJiECCS 'f INJECTION C? CAKCLNOGEHIC KTIB0CAR20NS : I - ,V * . a.-, tr.rsr.e i 2,--5er.=oyr;re , 1,2, 5, :-0i;sr:arr.-_r2- ce;;e - I;se,r^. Hu-s/c sr Nuscer A';g.latent 50* latent else, Carcino genic *ee<B ecK8 mo ex ^'.2C5. 2.0 0.25 ~. 5 1.0 2.0 0.23 0' .5-S . 2. C . 2.0 20 2; - 20 T * 9.Q 20 20 20 2C 2' 00 * y^ , *' 15, H 20 i? 13.8 20 2C 12.5 2C 20 12.1 19 2 l^T 9 24.6 23.4 203 19 17 il . 7 IS -5 13. S 3.9 5.0 '.3 3.6 13.3 11.6 11.1 11.1 20.6 20.3 ie.j 14.0 14.1 140 150 1 SC 140 90 100 115 120 50 . c* c so `X 5 ' fll w 33, I-S 5 Z >m X r * 5 5w n 3" g <n mr j v o v> - r or- rt ji oa ? -* rs --p -4 X i 1 U' ) ^/ STS 2520520 WATER_PCB-SD0000063251 fZ<7TZC7ZD MATETLKL . MO6lS>-ST0 IMS ORANGE CQyERA<3EUTXUT<Ott APFrsr: T". 6 3 P Z CTT.ID S '-LT1 i 3 p -*** . * _ - , -' '7 * ~ " V ' **" 17 7* \ n x *? 4 W * 5XR O 3 p sa5 gw nr 0j wW 4 n s**i O rny- > * ro 4^ \ i J j < i~ ; * A S sre :52052i WATER_PCB-SD0000063252 FKCTTC7EZ MaTEUAL MONSANTO INSURANCE COVJSaCZ LfflCATKX: " -Methyl -1, -benzanthracene , i V^V S-beniar.trjr&c -n*s benzanthracene \ O *4 mk ^ X * ^ W * 15 * m 3 3 * 3-9 n* r-- 3n >--> mM X* 8" wr 4 CO 0w - n =r 5, O9 >r Hx U) S N3 ;i STC :520522 t. WATER_PCB-SD0000063253 f I- __ ^OTSCTHTJ MAffiRJAL MON5A.NTO MI^ANCE COVERAGE IJTXSADON 5-Metr.yi-ii 2-bcnzaji-ftracene s4 a * w r ** oa rX x rH s a * a 3 sr> IgSa"r -4 Vj* -4 O s r a m> OB VM ; -y.etr.5xy- i. 2-bcnsar.tftraeere . .I ,-co: :-bensirtmss STC -520523 K3 4* LU II WATER_PCB-SD0000063254 PROTECTED MATERIAL MONSANTO QiSURANCX CX3VBUCEUTJGATJObl i Dlsetnyl-i.2-benzantftricne /?\ i .( -- .*. *i ;, '-Z-ZLzt'.r.y1 -1,2-bensar,b.w-3:sne ''vN^' ..-5 -Sen;a.-!:.".raiere .. 9-Dir.e v r,*5 v b#Rz&r.?r.r&cene -C.^5 --"o ; x:v - STS 252032^ 0 * **> *S jDH' 58W o 3 ^*"> c-i Om x * * s rM H5 - 5 i" nr -i H 0W hn s r* oc> a M rx * -1 * fS5 4* L/ WATER_PCB-SD0000063255 FRVlbLJJP COYBC^LmOAflON 19. 1,2,5, 6-dlbenxtuthracene 1 O4 *X4 ** 43 5n wS'- oaa-o3ww r-s >z m -X r 3 *4 m 5om IS" gr -4 *64 wcn -s4 nr* n 5. o > *4 r-- xa 3* cn $ fO * j ;r/) i. t ST6 ZHOU* L WATER_PCB-SD0000063256 PSOTBCTB? MATSUAL WQKSANTO XHSUSANCT CCVESA^LnXUTKtf 24 Mecnyl-3;i*-b*nxprrene O-* *x4 wn. -s!>!5***s4.' o3^ |p 5 z* m -X r h *n 2* Sn w- S" jnr -4 O4 tVrt) -x* nP` n 5. ox s > -4 -z *> 4 Z C/5 Metr.yl ".siaji'ir.rene A t 1 ST6 2520326 |/ WATER_PCB-SD0000063257 PUQTZCTW INSURANCE COYERA^UTiGAnON I 31. ::-X>'irc,v/-20-rei.n7icr,siaD'Er.r*r>e C-1 *X4 ** & 8 S' O -a 3mo m* S' > r a * n R - g VI n 4 rW*n O VI -4 O scn rn* J H r* sv -4 S e i r. o i &n - nr s r. e iS-Benzsehy H,C '------olan?r.rsne \ \ / :xv::: i STS 2520527 WATER_PCB-SD0000063258 protects material monsamto u^wawce gpysucELmGAnoN 35. 2, *3en2?nen&nt.w.rene 25. :-Me?.v/i- 2, i-benspr.eninr.'u-ere HqCS 2,4, 5,5-Diten2car2a.2 23. c,5.6-o;2en2cir=a20l.e 'VN;v\/^ 13* 3)Xit --DiSenz&cniine Q *4 -4 H* S = waw a 3 * 2O SR rX >X rMS am Sw - n -* n s ros 5m C5 -4< * )L xv STC 2520928 WATER_PCB-SD0000063259 ,TtOTCTD UAtmiAL-u<MSANTomsxMAMss, ocYmte^urt^mm no |5R^ 5oSn?* *5i g w ( 0 CO 11^ : ,. 4 '>* \ *`iWv a"? r* 3 iS -4 n s8 > * cs 3* i ) J ST6 2320329 I WATER_PCB-SD0000063260 TRANSCRIPT OF PROCEEDINGS - IN THE SUPERIOR COURT OF THE STATE OF DELAWARE IN AND FOR NEW CASTLE COUNTY MONSANTO COMPANY, Plaintiff, v. AETNA CASUALTY & SURETY COMPANY, ' " al., Defendants Civil Action Number 88C-JA-118-1-CV NON-ARBITRATION CASE KELLY DEPOSITION EXHIBITS PROTECTED MATERIAL: MONSANTO INSURANCE COVERAGE LITIGATION Washington, D. C. Thursday, February 4, 1993 ACE - FEDERAL REPORTERS, INC. Stenotype Reporters 1120 G Street, NW Washington, D.C. 20005 (202) 347-3700 NATIONWIDE COVERAGE 800-336-6646 WATER PCB-SD0000063261