Document nmDEw0LBoVqvojZOQ7myLpx3m

Instruction for Typing Abstract PLAINTIFFS EXHIBIT UC-889 Since the abstracts are to be reproduced directly from the author's own typescripts In photo-otfset, reed instructions carefully before typing abstract 1. Do not mak6 carbon oopies when typing on this form. 2. Use a typewntor, preferably electric, with ELITE type, black ribbon (preferably carbon). Insorlions should be written in BLACK ink. 3. Do not erase. Your abstract will appear in print EXACTLY as submitted. 4. ENGLISH should be used for submitting of any abstract. 5. Please make the abstract as informative as possible including methods, results and conclusions reached. It is not adequate to state: -The results will be discussed-. 6. Your entire abstract must fit within the box outlined. 7. Use abbreviations as far as possible to describe the names of laboratory or reference journals, for example, Biochem. Div., Nall. Inst, for Cancer Res., Biochem. Dept., Univ. of Oxford: J. Biol. Chem. 235.10 (1960). 8. Your abstract should be sent to the Secretary and should be received before April 30 1979 NOTE ESPECIALLY: Entire abstract In 1 paragraph typed single-spaced and no margin at top or left side. -* Title in CAPITAL LETTERS ' Author names underlined / Laboratory where research was done, city, state and country STUDIES"OT SeA-STOI!.VENOMS!' 'CHYSTm^SRElQTT OF 'ERXBDTOXIMS' 3 AND b FROM/LATICAUDA SEMIFASCIATA VENOM. N. Taisiya* & H.Arai**. *Chern. Dept., Tohoku Univ..Japan and Med.School, Tokyo Med. and Dent. Univ., Tokyo,Japan. The toxic principles in the venom of the sea-snake Laticauda semifasciata were separated into two components by CM-cel 1 ul oat- chromatography and obtained in crystalline forms by salting out with (NH^JgSO^. They were named 'erabutoxins a and b'. The homogeneity of each toxin was shown by rechromatcgi-aphy, by disc electrophoresis,by ultracentri fuging, by toxicity measurements before and after repeated crystallizations and by N-terminal amino acid analysis. They had molecular weights of about 7000 as measured by (Abstract may be extended to fill the rectangle.) A J L, 4 4 3 ftli if _L ti J/o THE INFLUENCE OF OCCUPATIONAL AND ENVIRONMENTAL ASBES TOS EXPOSURE ON THE INCIDENCE OF MALIGNANT MESOTHELIOMA IN CT. J.C. Lewinsohn, J.W. Meigs, M.J. Teta, Ct. Can cer Epid. Unit., Yale Uriiv. New Haven, Ct.06510, U.S.A. Medical, demographic, and occupational data were collected for the 229 cases of malignant mesothelioma ascertained by the Ct. Tumor Registry between 1935 and 1977 and for a random sample of approximately 700 de cedents (1935-1977) from the Division of Health Statis tics of the Ct. State Dept, of Health. Sources of in formation include the files of the CTR, death certifi cates, and city directories. A vital statistics tape of Ct. decedents was utilized to match spouses of cases An asbestos-product listing with its associated indus trial and employer codes has been created from the oc cupational histories of cases and controls. A substan tial increase in registrations of mesothelioma over this 42 yr. period is evident with 85% of the cases enumerated after 1954. Changes in patterns of diagnosis and the possibility of misclassification are suggested. Thi^ hypothesis is supported by: a) only ^0% of cases haveJa/.agnostic confirmation; b) discriminant function analysis performed on the 56 confirmed cases of pleural mesothelioma and the 20 cases of primary pleural tumors (not mesothelioma) with respect to age, sex, survival, stage, and number of tumors yielded 59% mis classif ication. Geographical clustering is evident in certain industrial cities and Labor Market Areas.I Final results will include case-control comparisons with re spect to occupational asbestos exposure, an analysis of the health status of spouses of these cases, and the occupational histories of spouses of non-occupationally exposed cases.| t A0045C [fe d*T(C \ "tUc. p<2*<>3. S? -ktc $*a ^ teue. * c&a JET> 9^^ ca/tc* <0/ 4^7? Ox*/^|^K^euM\ (~>^) , $fc< u&L&r? Q\A) ou^ {"Uaica* MjU^au2JbLivt^ unoleK u>uc ckuA^Au^cef l^2C**( '^17. t^iuCjLL^L_^W4 kflUf (^C2m aujfc) l^'~bj4ju' +e*^c!BM ti^tfuaas. ^ oj caJK/i a ^t*0LdBufrt^ 1 x[ *k> (y>0 Vki) luJl^Wi S%Jju^ auj) >0^b u-fcV' cm/ *^Cfe---LGJiXA "*&{1 U*Ui'<>r&*e*!<jV'iciL i[ P0M;--trc--ttttlfcu/u*) l*Jfc-U/iK> ---* \W aitaaELaU. *A OLtCL^&^j H &4 Ctu^ M J- 3 CUM-***-**"4 A o'>p';' / t ;rr; -I1 The Influence of Occupational and Environmental Asbestos Exposure on the Incidence of Malignant Mesothelioma in Connecticut b7 H. C. Levinsohn J. W. Meigs The Influence of Occupational and Environmental Asbestos Exposure on the Incidence of Malignant Mesothelioma in Connecticut.. by H. C. Lewinsohn, J. W. Meigs, and M. J. Teta Introduction Bruckman et al. (1977a) reported that "the combined sex ageadjusted mesothelioma incidence rate (AAR) per 100,000 Connecticut population has exhibited a possible ten-fold increase since 1935They acknowledge that the available statistics might be subject to diagnostic error but, nevertheless, postulate that the rapid increase in the State's mesothelioma incidence rate is closely related to the increase in the State's "cumulative asbestos consumption", which includes asbestos emissions from industrial sources, motor vehicles, and building demolition. One criticism of their study is the failure to make available complete occupational exposure histories for the 133 diagnosed (19351972) cases of mesothelioma drawn from the Connecticut Tumor Registry (CTR). The Air Compliance Unit of the Connecticut Department of Environmental Protection has monitored asbestos concentrations in Connecticut (Bruckman, 1977bJ Bruckman, 1978) and proposed an ambient air standard for Connecticut of 30^g/m^ measured over a thirty-day interval. The rapid increase in the State's mesothelioma incidence 2. reported in 1977 is referred to as justification for this proposal. The present study has been designed to re-examine the identified cases of malignant mesothelioma recorded in the CTR and attempt to determine the role of various etiological factors, such as occupational and environmental asbestos exposures. In view of the acknowledged possible diagnostic errors, which our results verify, a thorough review of available histological material will be undertaken. Methodology The CTR has identified 229 cases of malignant mesothelioma of the pleura (147) and peritoneum (33), other mesotheliomas, including breast, ovary, synovial membrane, testis, spermatic cord, perivesical tissue, cervical glands, brain, esophagus, bone and sternum (49), as well as 38 other pleural tumors, not mesothelioma, which were diagnosed in the state between 1935 and 1977 (Table 1). Disease topology and morphology are coded according to the ICD-0 (World Health Organization, 1976) classification. Medical, demographic, and occupational data have been collected for the cases and for their respective spouses. Similar information has been gathered for a random sample of approximately 700 decedents (1935-76) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health (Table 2). Descriptive epidemiology for this research pertains primarily to the forty-three year time interval. Statistical modeling and future A;\J' r' V./ f S U *> 3. case-control comparisons include cases (215) diagnosed after 195^ (Table 1), and controls (605) whose deaths occurred during this same time period. This procedure yields a oase-control ratio of approximately 1:3, while reducing sources of error resulting from the limited occupational and medical data prior to 1955 and the increasing awareness of mesothelioma associated with the later time period (1955-1977). The Price and Lee City Directories, utilized as an occupational data source for the three populations, were available for approximately sixty-six percent of Connecticut towns from 1890 to date ( with the exception of smaller towns). Directories were searched for job title and name of specific employer or industry for cases, controls and spouses at 1, 10, 20, 25, 30> 40 and 50 years prior to date of diagnosis, death or until the subject was less than twenty years old. An occupational history search was attempted for spouses to coincide with these intervals for their corresponding cases. The three-digit 1970 U. S. Census industrial and occupational codes (U. S. Dept, of Commerce, 1971) were assigned to the employment information ascertained from medical histories, death certificates, and City Directories. Industrial coding was determined on the basis of product descriptions for each specific employer which were found in the manufacturing directories of Connecticut, published by the State Department of Labor (1957* 1966, 1973) and from the Price and Lee Directories for non-manufacturing industries. From the complete listing of job and industrial codes a subset was selected by H. C. Lewinsohn, utilizing published sources indicating occupations A0045b 4. and products associated with asbestos (Hutchison, 1976; Levine, 1978; Weston, 1976)' This will form the basis for probable asbestos expsoure classifications. The City Directory data over five decades provides information on duration of exposure. With a categorical response variable of occupational asbestos exposure, two fundamental research interests can be tested: 1. Whether cases and controls differ significantly with respect to job-related asbestos exposure (Relative Risk) and 2. The nature of the relative contributions of occupation, spouse occupation and geo graphical residence to the incidence of mesothelioma in Connecticut (Logistic Regression). In addition, the health experience of spouses of occupationally exposed cases and spouses of non-exposed cases can be compared. Results Of all cases diagnosed as pleural mesothelioma, twenty-one percent t (31) had unknown staging (SEER, 1976) and sixty percent did not have an autopsy. The forty-nine cases of mesothelioma of other or unknown site have a mean age of fifty-two yeans and sixty-seven percent are without autopsies. The male-female ratio is approximately 1.5:1 (Table 3) The question of the accuracy of classification of cases of malignant pleural tumors into mesothelioma and other pleural tumors naturally arises. The mean ages and the male-female ratios are similar for these two groups and the "other pleural tumor" A0D453 5. group exhibits weak diagnostic confirmation, i.e., seventy-one percent positive histology and only thirty-five percent autopsied. A discriminant function analysis of these two groups of cases (diagnosed after 1954) on the basis of age, sex, survival, time, stage, and number of tumors yields a sixty percent misclassification. This result suggests that: 1. Either these variables are not sufficiently powerful discriminators of pleural mesothelioma from other pleural tumors, or 2. The two groups, as a result of mis-assignment of a substantial number of cases to the incorrect category, now lack the heterogeneity one would expect from distinct categories. If consideration is limited to cases identified after 1954, when recorded clinical detail in general improved, as well as an increasing awareness of this form of cancer, the number of cases with solid diagnostic confirmation and characteristics consistent with the natural history of mesothelioma are strikingly few. Of the 131 cases classified as pleural mesothelioma, 124 (95^) bad histological material, (specimen from biopsy, frozen section, surgery, autopsy or D and C) examined and autopsies were performed on forty-five cases (38/0* The proportion autopsied is disappointingly small. Table 4. shows the percentages of subjects with these two diagnostic critieria for mesothelioma cases of other or unknown site, for peritoneal mesothelioma, and cases of pleural tumors, not mesothelioma. A0O457 6. As a result of these findings, it is imperative that a slide review and a re-examination of hospital clinical reports for all cases of mesothelioma and other pleural tumors be undertaken. A commitment has been received from an independent pathologist for this aspect of the study. The following data analyses are subject to change subsequent to this procedure. Descriptive Epidemiology Between 1935 and 1977 > the CTE identified 229 cases of mesothelioma, yielding an overall crude incidence rate of i'aur per million. Age-adjusted incidence rates per 100,000 population (using 1950 U. S. population as a standard) for pleural and peritoneal mesothelioma consistently increase and exhibit a rapid rise beginning about 1955 .04 (1935 - 44)j .07 (1945 - 54); .18 (1955 - 64) (Figure 1.). We are in the process of generating these rates through 1977* Of these cases, 195 (85%) were reported after 1954. The male-female ratio is approximately 2:1; the mean age at diagnosis is fifty-nine years. Survival time from date of diagnosis to date of death is approximately ten months. A logistic regression model of the form: Log ^ ^ ) = A + X1 + X2 + X3 was fit in order to examine the incidence of pleural mesothelioma (binary response variable) as a function of the categorical explana tory variables - time, age and sex (X^, X^). Connecticut population figures supplied by the Connecticut State Department of Health were A used for denominator data in the estimate of disease probability (P). A00458 7. The three and two-way interactions of time, age and sex were found to be unimportant and the main effects model provided a reasonably good fit (p> 0.1). AAA From the estimates of the model parameters (B^, B^, B^), changes in relative risk (here approximated by the odds ratio) over time intervals, age categories, and sex groups are approximated. Persons exposed between 1975 - 77 carry 3*5 times the risk of pleural mesothelioma as those exposed between 1955 - 64. With progression across the age intervals: 45-54, 55-64, 65-74,...the individual risk of this disease is 1.5 times greater than in the preceding ten year age group. As one might expect, males have three times the risk of females. In assessing these results, the poor diagnostic confirmation outlined in Table 3 should be borne in mind. The geographical distribution of cases of mesothelioma throughout Connecticut shows evidence of urban clusters in the five largest cities where 30$ f the cases resided at the time of diagnosis. Since these locations have comprised from 3756 to 20% of Connecticut's population (1940 - 1977)> the suggested urban effect reduces to merely being a factor of population density. These five large cities are also centers of Labor Market Areas (LMA) of which there are eighteen in the State. Application of the CochranMantel-Haenszel Test of Average Partial Association (Landis et al., 1978) between these five LMA's and time of diagnosis (1935-77)> while controlling for population age differences, suggests the following: AG0453 8. 1. Incidence trends (i.e., the manner in which an area's cases distribute over given time intervals) are primarily the same for four out of five LMA's tested. One region suggests a greater proportion of its cases appearing in more recent years than the others (p=.04). This is readily explicable by the substantial in-migration experienced by this one area and its increasing industrialization as opposed to the other highly industrialized areas whose populations have gradually decreased over time and are, therefore, more comparable for analysis. 2. With the exclusion of this one LMA, the others indicate a similar distribution of their cases of mesothelioma over time (p=.17) This possibly implies similar patterns of asbestos exposure for the four large industrial regions of Connecticut. Until such time as the mesothelioma incidence has been adjusted for the previously mentioned diagnostic weaknesses and possible misclassifications and until the occupationally exposed cases have been identified, it is not possible to determine the role of environmental asbestos exposure, if any, in the remaining cases. Summary Medical, occupational, and demographic data were collected for 267 cases of malignant mesothelioma and other pleural tumors, their spouses, and 605 controls. Methodology was developed for classification of subjects into probable asbestos exposure categories on the basis of product and job descriptions. Although disease incidence rates * o 'w ^ AUU40C exhibit a rapid increase from 1955 to 19771 there remains a serious question of diagnostic reliability. A case review will be undertaken. 9. Acknowledgements The authors wish to acknowledge the technical assistance of Linda Mowad of the Connecticut Cancer Epidemiology Unit and Kathleen Pinto of Raybestos-Manhattan, Inc. A0045 1 10. References Bruckman, L., Rubino, R. A., and Christine, B. (1977a) Asbestos and Mesothelioma in Connecticut. APCA Journal. 27 121-126 Bruckman, L. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos: Definitions and Measurement Methods. National Bureau of Standards, Gaithersburg, Maryland Bruckman, L. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 28, 1221-1226 Connecticut Labor Department: Directory of Connecticut Manufacturing and Mechanical Establishments (1957) Wethersfield, Connecticut Connecticut Labor Department: Directory of Connecticut Manufacturing and Mechanical Establishments (1966) Wethersfield, Connecticut t Connecticut Labor Department: Directory of Connecticut Manufacturing and Mechanical Establishments (1973) Wethersfield, Connecticut Cox, D. R. (1969) The Analysis of Binary Data: London; Methuen and Company, Ltd., pp. 14-29 Hutchison, M. K. (1976) A Guide to the Work-Relatedness of Disease. Washington, D. C., U. S. Department of Health, Education and Welfare (U. S. Government Printing Office) A00462 11. Landis, R. J., Cooper, M. M., Kennedy, T., Koch, G. G. (1978) A Computer Program for Testing Average Partial Association in ThreeWay Contingency Tables (Parcat) Biostatistical Technical Report #18 Levine, R. J. (ed.) (1978) Asbestos: An Information Source. Washington, D. C., U. S. Department of Health, Education and Welfare (DHEW Publication Number (NJH) 79-1681) Price and Lee City Directory (1890-1977) The Price and Lee Company, New Haven, Connecticut U. S. Department of Commerce, Bureau of the Census: 1970 Census of the Population. Alphabetical Index of Industries and Occupations (1971)> Washington, D. C., TJ. S. Government Printing Office U. S. Department of Health, Education and Welfare, National Cancer Institute Cancer Surveillance Epidemiology and End Results Reporting. SEER Program (1976), Washington, D. C., U. S. Government Frinting Office Weston, R. F. (1976) Technical Feasibility and Economic Impact of OSHA Proposed Revision to the Asbestos Standard. Prepared for the Asbestos Information Association/North America. Washington, D. C., Figure 2-1, p. 2-3. World Health Organization: ICD-0 International Classification of Diseases for Oncology. (1976) Geneva, Switzerland A00463 12. Hilton C. Lewinsohn,Corporate Medical Director, Raybestos-Manhattan, Inc. and Lecturer, Yale School of Epidemiology and Public Health (address: Raybestos-Manhattan, Inc., 100 Oakview Drive, Trumbull, Connecticut 06611, U. S. A.) J. Wister Meigs, Director, Connecticut Cancer Epidemiology Unit and Clinical Professor of Epidemiology, Yale School of Epidemiology and Public Health (address: 30 College Street, New Haven, Connecticut 06520, U. S. A.) Mary Jane Teta, Associate in Research, Connecticut Cancer Epidemiology Unit, Yale School of Epidemiology and Public Health (address: 30 College Street, New Haven, Connecticut 06520, U. S. A.) A00464 Figure 1 Age-adjusted Incidence Rates by Decade of Diagnosis, Pleural and Peritoneal Mesothelioma, Connecticut, 1935 - 197^ A0046b e0+ *T03 oo ooo o-p- o00 tr-o> On iou P0 -p- DECADE OF DIAGNOSIS ACO435 Table 1. CTR Reported Cases of Mesothelioma and Other Pleural Tumors Diagnosed Between 1935 and. 1977 Table 2. Sources of Data and Variables Table 3* Sex, Age and Diagnostic Characteristics of Malignant Mesothelioma Cases and Other Pleural Tumors Diagnosed in Connecticut, 1935 - 1977 Table 4 Diagnostic Evidence for Disease Groups A004n 7 Table 1 Diagnosis Period 10*5-77 Primary Pleural Tumors (T6^) 185 Mesothelioma (M905) Other 147 38 Peritoneal Mesothelioma (T58, M905) 33 Mesothelioma Elsewhere 49 Site not pleura or peritoneum Site unknown (T99) 37 12 t 267 267 Period 1955-77 151 131 20 29 35 27 8 215 215 A 004 68 v iH cd o H c H f--1 C o H P -p 03 G o TO oco 1, 0} O H rH & E TO O H V (X P G 21 US to o O r--1 B r-1 <D O Q <M V X! -P aJ T) M o TO TO G G O V O S to -P H u JS TO P OG Vl X! M -P O GTO sTO o T3 Xi p GTO rG G B <P G OG TO TO TO TO s G O O a. TO y to % rH -P Xc p TO G Vi f. 00 O O rH BP CD Q sTO TO H Cm iH OTO P G Vi O Cm TO G O H -P P H U TO TO TO Q TO Vl P TO TO > Go T> rH OP I TO TO u TO o Vi <H TJ TJ TO GG t O H TO -P TO B a P H VTOi G Vi ( TO Oo TO rH TO TO P G o B o TO p -P TO TO 00 G TJ S rH O Vi 2 Vi G H P -P -P O H -P G C H C TO S 5 rH O B TJ iH 1 T3 P G H S BTO O G TTOO T) O u -p T3 G M *y TO TO T3 O o JQ O *"9 CD CO xf^__ > O / Variables Population 03 0caa1> CO o2 2 P< o CO TOr rH O Vi -P oC o TO TO TO 03 o G 03 2p CJ> CO y TO rH O Vi -P oG o v 03 TTTOOO o0) G 03 03 p O CO TOy rH O Jh P G O o 0a>3 03 TTToGOOO 2P o CO y TO -P GB rH TO G H 'iOH G TO P P TO a Vi ---y Cu cd Ph y -rH P p o *y TO CO c-- On rH | <H 8 TO OGB LT\ on p< GG os 2 Eh Mr> 5C Ph cd Eh G TO TO --TO TO rH a TO -P 03 TO TO -P 03 H O H G O G O G O W) P P H ca ^2 TO Cm 25 H P P H #y H P P O cd 3 TO pO Vi TO s CO G G O Eh TO TO rH JS T3 JS PO 03 PH > -OP GS TrTHOO Vi -P G QSi -P G a H -P TO TO 2 o o Cm O TO TO rH Vi O -PTTOO Vi tH m a r~ Os bo r--l GH y Vi MO G vO -P Os TO rH G Cm G 3 s ITS Ov rH TTOO rH Vi O -P TO TO Fh H Q > P H O TO TO h4 TJ 3G TO THO PU *k> TO rH O U P oC o TO s 03 TTOO a> G CO O cd P u CO TS c cd rH a3 H P P 03 2 T3 c H 03 03 Q) 2 T3 0c3 O O Q o iH 2c CO O H P G> 2 ro- Ph 2 O iO--si o o Source > t3 0a. 00 vi. o VI LT\ m Ov co vms. m 5 -=j" 0 S43* Vi. Vi. Vi. -P 01 rn rH j- J- H *H Ov r- Ov CO Oo0n1 X b0) c VO 0 Sa; CO CO vO u~\ CM u"\ Vi. co 00 iOrvv mo rH CO CO Ov 0 rH S COO J- CO o CO Ov CO LTV r- i\ ri--i croo mro oj-v r-- VcOo ,--.. o3 -P 0 0 s o es 0 o cO rH O 0 cj 50 m oO 0 01 H H --' tH rH rH 0 *H 0 rH H rH 43 H .s Q rH 0 rH 0 C0 0m O 0 si 0 X! O XI si U +5 ga) 3 o 3 oo m 0 ra -P 43 OHi Oa 43 fn O0 ra .c -p - s oH rH 0 rH 0 00 Q OH JS OH 2 PH SS 43 H 01 r0H5 -P O Eh ON .Ou0 s 'O rH 0 OHn oO0o VrO- Ov WwH A 0 0 4 /q Table 4. Diagnosis Peritoneal Mesothelioma No. 29 Other mesothelioma (not pleural or peritoneal) 35 Pleural tumors, not mesothelioma 20 "Positive Histology'*'*'* Autopsy 9656 88% 88% k0% 85% 36% 1. SEER, 1976, Code/Field Number 19 A00471 TITLE: I lie Influence of Occupational and Lnvi I'onmenta 1 Asbestos Exposure oi tlie Incidence of Malignant Mesothelioma in Ct: A Retrospective Case Con trol Study Investigators: J. Wister Meigs, Director, Connecticut Cancer epidemiology Unit and Clinical Professor of Epidemiology, Yale School of Epidemi ology and Public Health iiilton C. Lewinsohn, Corporate Director, Raybestos-Manhattan, Inc. and Lecturer, Yale School of Epidemiology and Public Health Research Plan 1. Specific Aims j>f this Investigation . a. To evaluate the extent of misclassification of malignant pleural mesothel ioma and other primary pleural tumors in Ct. from 1935-1977. From the en tire set of primary' pleural tumors a homogeneous subset will be selected on the basis of clinical, pathologic, and histologic criteria most repre sentative of pleural mesothelioma. Comparisons will be made of these cases and those originally classified as pleural mesothelioma. b. To bring up to date the descriptive epidemiology of all mesothelioma (pleural, peritoneal, other) and other primary pleural tumors. c. To make case-control comparisons of occupational exposures, controlling for age, sex, and population density. Occupational histories of the popu lation group under study will be collected in terms of job type, place of employment, and product of place of employment. Risk associated with occupational exposure of short duration will also be assessed. d. To examine for non-occupationally exposed cases and controls the extent of risk associated with low-dose environmental exposure by utilizing information relative to occupational history of spouses and geographical distance of homes from places of asbestos manufacturing. e. To assess the effect of occupational asbestos exposure on the disease experience of spouses. 2.Future Research Objectives a. To examine the incidence of lung cancer, gastro-intestinal cancer, and cancer of the larynx and other cancers in Ct. in order to see whether there is any correlation between them and malignant mesothelioma in the various geographical locations which could be usefully applied to esti mate the public health risk, if any. / A00507 1). To re-v iota mesotheliomas o4~ all sites 'or possible relationship to asbestos in water supplies both at home and at place of employment. Cases with out evidence of exposure from aiiii.i nt air, occupation, or spouses' occu pation can be examined regarding the waterborne asbestos hypothesis. c. To examine the relationship of asbestos fiber type arid mesothelioma by studying the extent of geographical clustering of this disease about manufacturing firms whose products have known concentrations of crocidolite, chrvsotile, and amosite. A 005 08 Till: PROHI.Bt: Studies of occupationally exposed populations have clearly demonstrated the health hazards associated with exposure to asbestos and asbestos products. (Doll, 1965; Mancuso and El-Atar, 19(7; Wagiier et al., 1960; Newhouse ar.d Thompson, 196.'); McDonald, 1973; Elmes, 19<5J Three major lesions have been identified, namely, pulmonary fibrosis (asbestosis), lung cancer, and djffusc malignant mesothelioma of the pleura and peritoneum. In addition, an excess of deaths due to cancers of the gastro-intestinal tract have been reported in some studies and an association between asbestos exposure and laryngeal can cer has been demonstrated. It has been postulated that there may also be an increased risk of brain and renal cancers in asbestos workers but the epidemiological evidence for this is as yet unproven. Thus far, the only positive evidence of ron-occupational exposure is from living in close proximity to asbestos mining operations or factories with inadequate dust controls, and in a few isolated instances from domestic sources of contact with the clothing of relatives, friends or lodgers who were asbestos workers. Malignant mesothelioma has resulted from such exposures, but the number of such cases reported in the world literature remains very smal1.(Kagner et al., 1960; Newhouse, 1965; Champion, 1971; Selikoff and Hammond,1967, 1969) There has been great concern in recent years about a public health risk from asbestos in the general environment, but at the present time there are no data available to substantiate or refute this fear. The presence of asbestos fibers in water, beverages, drugs, and the ambient air has not been correlated with disease in the general population. In all published series of mesothelioma, there is a small proportion of cases where exposure to as bestos is considered unlikely or impossible (.McDonald et al., 1970; Webster, 1972; Greenberg and Davies, 1974; Milne, 1976), but in some cases this depends upon the care with which the evidence of exposure is sought for.Another source of confusion in the attempt to isolate causative factors in the development of mesothelioma is the different biological effects of vaxioustypes of asbestos fibers.(McDonald,1978) Crocidolite asbestos from certain regions appears to be the most likely to produce this disease, whereaschrysotile is least likely to do so and amosite (cummingtonite-grunerite) holdsa doubtful intermediary po sition. On the other hand, the possibility that mesothelioma may be incorrectly attributed to asbestos exposure, must also be taken into account.In 1978 the suspicion that other materials could be partly responsible for those cases without known exposure to asbestos, was apparently verified by the finding in Turkey that asbestos related diseases mainly calcified pleural plaques, chronic fibrosing pleuritis and malignant pleural mesothelioma are endemic is some villages without asbestos deposits. These fibers were shown to be erionite type zeolite. Thus it would seem that fiber-shape and size is important in the etiology of malignant mesothelioma and fibrous minerals from sources other than asbestos mining or processing may be implicated in the epi demiology of this disease.(Baris et al., 1978) A 005U 9 The reported frequency of mesothelioma has substantially increased in Ct. in the late 1950's and has continued to increase steadily since that time.One possible explanation is increased recognition <n the part of pathologistsanJ clinicians as to the existence and etiology of this disease. It has also been suggested that this increased incidence 'an be attributed to the tremendous growth of tin asbestos industry in ti e I..S. In view of the long lateru> per iod for the development of mesothelioma (Selihoff, 1977; Greenberg, 197-1) a continued rise in incidence until at least the end of tins century is a real fear expressed by someinvestigators. When the reported measurements of ambient air are studied in the literature, we see that even the highest figure for contamination of the genera) atmosphere is three orders-of magnitude below the current hygiene standard. In consid ering the public health risk we must not forget the great and continuous im provement in dust control in most workplaces where asbestos is used and, there fore, a decreasing emission of dust from these sources. The emission of fibers from brake linings has been cited as a source of asbestos in ambient air anJ, in Ct., such measurements as have been made, indicate that this may raise the background level where traffic is dense, where brakes are applied such as toll booths or traffic intersections. (Lruckman and Rubino, 1978) Earlier studies suggest a significant risk associated with low-dose expo sures resulting from geographical residence, occupation of spouse, or occupational exposure of short duration.(Wagner et al., I960; Selikoff, 1965; Anderson, 1976; Newhouse, 1972; Champion, 1971) A very recent publication (Whitwell et al., 1977) reports the amount of asbestos fibers in lung tissue to be associated with occupation but not with environment. No geographical cluster about asbestos manufacturers, independent of occupation, could be demon-strated. This study provides additional evidence that the development of asbestos-induced mesothelioma is dose related, an encouraging result in the evaluation of risk in the general environment. The question which remains unresolvedis whether the minute quantities of asbestos measurable in the ambient air contribute to the incidence in the general population of those diseases which have been identified in association with asbestos exposure in occupational situations. By examining in depth the mesothelioma cases which have been reported to the Connecticut Tumor Registry between 1935 and 1977 and investigating their background, if there is indeed a public health risk it should be brought to light. A005 i C MATERIALS AN!' METHODS: Cases will be comprised of all malignant mesotheliomas, both pleural and peritoneal, with positive histology diagnosed in Ct. from 1935-77, with the possible addition of some or all other malignant primary pleural tumors with similar characteristics. The maximum number of cases for the study would be 248 - 210 cases of mesothelioma, 38 cases of pleural tumors, non-mesothelioma. Cases from 1935-77 will be analyzed descriptively only. Those from 1955 on (approximately 116 - 98 mesothelioma, 18 non-mesothelioma pleural) will re-ceive formal statistical analyses including comparisons with a contrcl group of about 232 randomly selected deaths from the State of Ct. Department of Vital Statistics.(Table 1) t EXPECTED FINDINGS: An estimate of the relative importance of various sources of asbestos ex posure on the rising incidence of mesothelioma in Ct. is anticipated as a re sult of this research. The effect of changing trends in diagnosis and classi fication of this disease should also be suggested. Analyses based on cases cor rected for this effect will assess the level of risk associated with low-do-c exposure, namely, that which might result from residential proximity to as bestos manufacturing, an occupationally exposed spouse, or an occupational ex posure of short duration. 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