Document RjEo2LmkKzJ0nrng449Y3vvwn

Monsanto Mvmtma Csmimv 00 H. UMHrth SPht.*n<: 014J 884-10*030r September 15, 1982 Mr. David P. Brown Aaaiatant Chief Industrywide Studies Branch NIOSH 4876 Columbia Parkway Cincinnati, Ohio 4S226 Daar Dava: Enclosad ia tha Zack and Muach papar that w diacuaaad ovar tha talaphona. Any final draft of thia will diffar in tha background aaction but not in tha numbara in tha tablaa. Since EPA haa thia draft and ainca it waa rafarrad to in EFA's mini-symposium I aaa no problam in.summerixing tha raaulta for Dr. Wade, but I would prafar that you not aand him a copy just in caaa a alightly diffarant varaion gata publiahad. Yours aincaraly, aw Enclosure 86U William R. GMfsy, Ph.D. Managar, Epidemiology HONE 004075 A Retrospective Mortality Study of Polychlorinated Blphtnyl Manufacturing Workers^ Judith A. Zack, M.P.H.2 David C. Husch, M.P.H., Ph.0.3 ^Monsanto Company Departaen-t of Ksdiclnt and Environmental Health ^Present address: 1751 legend Lane St. Louis, MO 6314-1 Present address: Department of Ophthalmology University of Michigan Medical School ST2512 Scott Turner 31dg., Box 004 1010 Hall Street Ann Arbor, MI 48109 HONS 0040 76 O'J. il A . Abstrac A retrospective cohort mortality study of workers exposed to polychlori. natad biphenyls {PC8s) during production of the compounds is reported, A total of B9 workers exposed to PCBs for minimum of six months during the period from 1945 to 19S5 were followed through 1977, and their vital status was dtttr. mined. Comparison of this PCB-exposed cohort's mortality experience with age-, race-, and cause-specific mortality rates of the U.S. melt population was performed. Observed deaths were not statistically greater than expectad for any of the cancer sites examined, no deaths were observed for cancer of the liver or malignant melanoma. A statistically significant excess of circulatory disease deaths, exclusive of arteriosclerotic heart disease, was observed In white males. HONS 004077 Judith A, Zjc*/3aje 3 The term "polychlorinated biphenyls" (PCBs) describ S a group of mixed :hlorinated biphenyls which vary In consistency from light, free-flowing liquids to crystalline and non-crystalline solids, depending on the degree of chlorination. PCBs have been In commercial use since 1929. Their dielectric properties, resistance to oxidation, acids, bases, and other chemicals, and thermal stability have made them useful for many applications, particularly in the production of capacitors and transformers, and In the Insulation of elec tric cables and wires. Reports of adverse health effects In man initiated from several -Incidents of accidental heavy exposure to PCBs. A process change In a chemical plant Introduced an unspecified PCS compound (Arochlor) into the work environment, resulting in exposure of 14 workers to estimated breathing zone PCS levels of 0.1 mg/m^.l Chloracne developed In one-half of the exposed workers, and liver function tests showed a borderline abnormality In one of the seven affected workers. After 13 months of follow-up. the chloracne hid disappeared, but the liver function abnormality, although improved, remained. Accidental Ingestion of rice oil contaminated with PCBs has resulted in several outbreaks of common sjmptcmatolo$r, reported from Japan ("Yusho" disease)2 and Taiwan {'Tu-Cheng" disease).3 the most common acute symptoms observed were hyperpigmentation and acne-like lesions, discharge from the eyes, neuroendocrine disturbances, tmesis, and diarrhea. There was a dose-response relationship between the amount of oil ingested and the proportion of person: reporting symptom. After six years, many of the patients still reported such symptoms as headache, stomach pain, nunbness of the extremities, arthralgia, ind respiratory symptoms.* Although massive ingestion of PCBs occurred In these Incidents, analysis of the cooking oil in the Yusho episode shaded that. HONS QQAQ78 Judith A. ZjOt/Pig* olychlorlnatpd dlbeniofurans0 and polychlorinated quaterphenyls^ were co contaminants. Analysis of blood samples from patients in both incidents, as well as liver and adipose tissue from Yusho patients, showed the presence of these compounds along with PCBs.7* 0 These co-contaminants obscure the rela tionship of PCBs to the symptoms resulting from Ingestion of the contaminated rice oils. The Yusho incident served as a stimulus to a large number of toxicologi cal studies dealing with the health affects of PCBs. Chronic toxicity studies of PCBs In mice and rats have shown hepatic effects ranging from hyperplasia to well-differentiated hepatocellular carcinomas following the ingestion of various PCB-contalnlng diets.9* 1 Studies of hunan exposure to PCBS have shown that body burdens are directly related to the level tf exposure to PCBs.13 Morbidity-studies have focund on the effects of PCBs on the skin, liver, blood chemistry, and other systems.13. IB Chlcracne, dermatitis, mild liver func tion abnormalities, and increased triglycerides levels were reported with some consistency from these studies. Mortality studies of occupationally-expcstd individuals have not yielded consistent results. A preliminary report17 addressed an increase in deaths due to malignant melanoma (Z obs. vs. .0.04 exp.), which occurred in a group of 51 research and development and 41 refinery workers at a Hew Jersey petrochemical plant. Another author commented on problems in defining exposures in this study.10 In a study of Z567 capacitor plant workers exposed to PCBs.19 excesses of liver and rectal cancer deaths, which ware not statisticelly sig nificant, were reported. Although few deaths were available for analysis by duration of exposure and latency, there wa; no trend by these measures for liver cancer deaths, and a slight increase by latency but not by length of HONS 004079 Judith a, Zack/?aga 5 exposure for rectal cincir deaths. Another study of 1310 worker* from a capac itor-manufacturing plant with at least six months enployment between 1946 and 1970 found statistically significant excess deaths from all cancers (In males) and all causes (in females).20 Suggestive, but not statistically significant, excesses were noted for deaths due to digestive system cancers (in males) and malignancies of lymphatic and hematopoietic tissue (In males and females). >io deaths were attributed to liver cancer or malignant malanoma. Due to the rela tively young age of this worker cohort and the rtsultant small number of deaths (n * 27), site-specific excesses were based on two or three deaths; therefore, further study of this cohort was proposed by th authors. At about the time of the Initial report dealing with the mortality experi ence of an occupationally-exposed worker cohort, a preliminary review of the mortality experience of Monsanto workers Involved In the production of PCBs was carried out. The present study represents a completed analysis of this worker cohort's mortality, with particular attention given to overall cancer, liver and pancreatic cancer, and malignant melanoma. Materials and Methods During the period from 1936 to 1977, PCBs were manufactured at Monsanto Company's Sauget, Illinois plant. Throughout this period, the process of manufacture remained relatively unchanged. This process, In brief. Involved the bitch chlorination of biphenyls in the presence of Iron and iron chloride catalysts. The crude mixture proceed in the chlorlnators was than aerated, distilled, earth treated, filtered, and transferrsd to storage tanks before shipping. While no industrial hygiene monitoring data were available to quan tify the PCB-exposure levels during the stuoy time, interviews with plant personnel established the fact that PCB exposure levels did not vary consiesrably within the PCB department. Therefore, all workers in this department HONS 004080 Judith A. 5 wirt considered to have comon exposure to PCSs, as well as other chemical: usad In the dtpirtmint, Including hydrochloric add, trl- and tetrachloroben2*ne. biphenyl, and chlorine gas. All male employees fro* the hourly roll who worked In the PC3 department for at least six months between January 1, 1945 and December 31, 1965 were selected for the study. By use af the plant's computerized work history system, union record;, and manual work history verification, 89 male, hourly employees met the criteria for inclusion in the study. The vital status of 98.94 (88) of the cohort was determined as of December 31, 1977, using standard follow-up techniques. Table 1 summarizes the results of the vital status tracing. A death certificate was obtained for each person found to be deceased, and coding of the underlying cause of death was performed by an experienced nosologlst, using the International Classification, of 01 seises,-Adapted, Eighth P.*vis4on.Zl Using a computer program developed for such an application,22 the observed number :f deaths among PC3 workers was centered with those expected based on age-, race-, and cause-specific mortality rates of U.S. males. To compute ex pected r.umbars, person-years of observation were allocated to five-year age ar.d calendar time categories and rul tipi led by correspondlng race- and causespecific death rates for U.S. meles. The resulting quantities were summed ever all ages and years to obtain the total expected numbers. Ratios of ob served to expected niober of deaths were expressed as stindardlied mortality ratios (3rt?j). Significance testing of the SMRs was performed at the 54 level, assuming that the observed number of deaths follow a Poisson distribution.^! Results Of the 6a PC8 workers for whom vital status tracing was successful. S3 were verified living and 30 were verified deceased. Death certificates were MQNS 004081 Judith a. Iacit/?43e 7 obtained for each of tht decedents. The person-years of observation contri buted by the entire worker cohort are shown In Table 2, A total of UQQ.l person-years were observed at all ages, with the majority observed In the middle-age range (ages 3S-SO yrs. contributed 74%, or 1333.1 person-years to the total). Cross-classification of PCB exposure duration with vital status (Table 3) shows that the majority of both living and deceased workers were exposed less than three years. The average length of exposure to PCBs for living and deceased workers was similar, with deceased workers having slightly more exposure time (3.7 yrs. vs. 3.2 yrs., respectively). Cause-specific SMRs are listed In Tables 4 and 5 for the 60 white and 29 nonwhite male members of the PCB study cohort. Deaths due to malignant neo plasm, as indicated In Table 4, accounted for 27? (8) of the total nunber of deaths. Ho cancer deaths were attributed to malignant neoplasms of the liver or pancreas, or malignant melanoma. While many of the cancer-speciflc SMRs exceed 100, none are statistically significant. In white males, lung cancer accounted for 75? of the deaths dua to malignant neoplasms, while no single cause predominates In nonwhite males. Table 5 presents a brief summary of the eight caacer deaths In tht PCB worker cohort. Among the non-aialIgnant causes of death (Table 6), diseases of the cir culatory system accounted for almost_half of the deaths. For the category of circulatory system disease, exclusive of arteriosclerotic heart disease, the SMRs for white males and for tha total cohort wera significantly greater than 100. Tha excess in deaths due to this category Is accounted for solely by the experience of the white males, since nonwhite males showed an Smr of 93. no other causes of daath In Table 6 showed observed deaths whieh were statistical HONS 004082 Judi in a. Zack/^a,]! C greatsr than expected. The overall SMS for malignant and non-mall;nant causas his 131 (30 observed, 22.83 expected deaths), little difference was found in this overall SMR by race (for whites, 133; for nonwhites, 128). Discussion This investigation dealt with the mortality experience of a cohort of 09 nale workers Involved for a least six months In the production of PCBs between January 1, 1945 and December 31, 1985. The only cause of mortality which showed a statistically significant excess In observed deaths was circulatory diseases exclusive of arteriosclerotic heart disease. This excess was apparent only for white males. Circulatory diseases In this category included deaths from rheumatic heart disease, cerebrovascular disease, and other forms of heart di seas*. If this excess cause of death Is not an artifact, one would postulate that there nay also be a relation between risk factors of these circulatory diseases and PCS exposure. Blood pressure, a risk factor (when elevated) of coronary heart disease (CHD) and cerebrovascular disease, has been related to bicod ?C3 levels In two studies, with conflicting results. One study2* found that serum PC3-levels made a statistically significant contribution to explaining the varicblllty of diastolic (but not systolic) blood pressure measurements in multiple regression analyses of data from a conmunity exposed to DOT and PCBs, while another study* found no such association. Studies of lipids, which have been associated with CHD and (with less consistency) with cerebrovascular disease, have considered totel cholesterol, high density lipoprotein (HOI), art triglyceride levels in relation to blood PCB levels, while no consistent association has been shown between blood PCOs and tota1 cholesterol or HOI levels, most,13- 16 but not all,24 studies have shewn increased triglyceride HONS 004083 Judi tn A. Zack/Pjg* g levels with increased blood PC8 levels. Given the lack of support for an association between PCBs exposure and non-ASHD circulatory system deaths from previously reported mortality studies, and the inconclusive relation between cardiovascular risk factors and blood PCBs, this excess cause of death itust be viewed as a preliminary finding, In need of support from other studies. While previous mortality studies as well as toxicological studies have Implicated a variety of cancers - digestive system, liver, pancreas, malignant melanoma - as possible results of exposure to PCBs, the present study provides no support to such findings. In the Monsanto worker cohort, no deaths were attributed to liver or pancreatic cancer, nor were any malignant melanomas found. The overall excess In cancer deaths, while not statistically signifi cant (8 observed, 4.46 expected, $MR * 1791, Is mainly a result of respiratory cancer deaths In workers for whom smoking habits ware not ascertained. Although the present study's results db not support a carcinogenic effect associated with PCB exposure, there are significant limitations to the results. A principal limitation Is the slxe of the worker cohort, which prevents th* detection of Increases In risk to deaths from rare dlstasas. A nuch larger cohort followed for a longer period would be necessary to detect a two-fold Increase, for example, In observed liver cancer deaths. In order to allow for a latency period, the study cohort was limited to those working at least six months until Oecembtr, 1965. Sinee PCB production continued until 1977, further follow-up of the aiortallty of Monsanto's PCB-exposed workers will have larger numbers, as well as longer follow-up time. Another limitation common to retrospective studies of occupational cohorts is lack of knowledge of exposures from other work-related activities, while personal habits, such as smoking and drinking, can sometimes be roughly ascer tained if eo-workers or family members arc available for Interview, previous HONS 004084 Judi tn A. Zadc/Pjg* 13 exposures, or concurrent occupational exposures during follow-up, art ofttn impossible to assess. Tht connection of an affect to a previous PCS exposure oust first consider other potential effect-related exposures. A useful comparison group In occupational mortality studies Is an untxposed Industrial cohort, from the same plant. If possible. Ascertainment of mortality of such a cohort allows for comparison of SHRs between exposed and unexposed cohorts, which reduces the possibility that an elevated cause of death In the exposed cohort Is a result of a generally greater than expected cause-specific mortality In that tree or Industry. Such a comparison group would have been useful In evaluating the elevated mortality due to non-ASHO circulatory system diseases found In this study. (liven the slxe of the study cohort and the other limitations dtscrlbtd above, the results of this analysis of PC3-exposed worictrs1 mortality experi ence are not definitive, but rather contribute to the health-effects risejrch cn PCBs. A future study of this cohort could evaluate the mortality of wor'ters Involved frcn the Initial through the final year of PCB production, and thus have mors power to detect any possible hazards of PCB exposure. HONS 00*085 Judith A. Zack/pj;* j References 1. Meigs, J.W., Alboa, J.J*, Kartln, B.l. Chloracne from an unusual exposurt to Arochlor. J.A.M.A. 154:1417-1418, 1954. 2. Kuratsune, H., Yoshlmjra, T., Matsuzalca, J., Yamaguchl, A. Epldaml olostudy on YUsho, a poisoning causad by Ingtstlon of rlct oil contaminated with a commercial brand of polychlorinated blphefiyls. Environ, health Persp. 1:119-128, 1972. 3. Chang, K.J., Cheng, J.S. Huang, P.C., Tung, T.C. Study of patients with PC8 poisoning. 3. Formosan Med. Assoc. 79:304-313, 1980. 4. Urabe, H., Koda, H., Aiahl, M. Present state of Yusho patients. Ann. H.Y. Acad. Scl. 320:273-276, 1979. 5. Hagayama, J., Kuratsune, M., Masuda, Y. Determination of chlorinated dlbenzofurans In Kanechlors and *Yusho oil." Bull. Environ. Contam. Toxicol. 15:9-13, 1976. 6. Kamps, L.R., Trotter, W.J., Young, S.J., Carson, L.J,, Roach, J.A.G. , Sphon, J.A., Tanner, J.T., McMahon, 8. Polychlorinated quaterphenyls Identified In rice oil associated with Japanese "Yusho* poisoning. Bull. Environ. Contam. Toxicol. 20:589-591, 1978. 7. Kashlaoto, T., Mlyata. H., Kunlta. N. The presance of polychlorinated quaterphenyl* In the tissues cf Yusho victims. Food Cosmttics Toxicol. 19:335-340, 198L B. Kashlmoto, T., Mlyata, H., Kunita, S., Tung, T.Cj^Hsu, S.T., Chang, K.J. Tang, S.Y., Ohi, S., Nalcagawa, J., Yamamoto, S. Role of polychlorinated dibenzofuran In Yusho (PCB poisoning). Arch. Environ. Health 36:321 326, 1981. MOMS 004086 Judith A. Zac*/Page 12 9, Kimbrough, R.D., Under, R.E, , Gaines, T.8. Morphological changes In liver* of ret* fed polychlorinated biphenyl*. Arch. Environ. Health 25:354-364, 1972. 10. Itlmbroujh, R.O. , Squire, R.A., Under, R.E., Strandberg, J.O., Montali, R.J., Burse, V.W. Induction of liver tunors in Sierman strain female rats by polychlorinated biphenyl Arochlor 1260. 0. National Cancer Inst. 55:1453-1459. 1975. 11. Ouw, H.K., Simpson, G.R., Slyali, D.S. Use and health effects of Arochlor 1242, i polychlor.inited biphenyl, in an electrical industry. Arch. Environ. Health 31:189-194, 1976. 12. Haronl, H,, Coloabi, A., Cantoni, S., Ferioli, E., Foa, Y. Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environ, mental and blood polychlorinated biphenyls concentrations. Brit. J. Industr. Med. 38:49-54, 1981. 13. Chase, K.H., Wong, 0., Thomas, 0., Barney, B.W., Simon, R.it. Clinical and metabolic abnormalities associated with occupational exposure to polychlor inated biphanyls (PCBs). J. Cceup. fed. 24:109-114, 1982. 14. Fischpein, A., Wolff, H.S., Lilis, R., Thornton, J., Stlikoff, I.J. Clin ical findings anong PC8-txposed capacitor manufacturing workers. Ann. H.Y. Acad. SCI. 320:703-715, 1979. 15. Mircnl, M., Oolorsbl, A., Arbosti, S., Cantoni, S., Foa, V. Occupational exposure to polychlorinated biphenyls in electrical workers. II. Health effects. Brit. J. Industr. fed. 38:55-60, 1981. 16. Bakor, E.L., Jr., lindrigan, P.J., Glueck, C.U, lack, M.M., Jr., Uddle, J.A.. Burse, V.W., Houseworth, W.J. , Needham, l.l. Metabolic consequences of exposure to polychlorinated biphenyls (PC3) In sewage sludge. An. J. Epidemiol. 112:553-563, 1930. HONS 00*1087 Judith A. Zack/Page 13 17. Bahn, A.K., Rostnwalke, I., Herrmann, H., Grover, P., Stallman, j,f O'Leary, K. Melanoma after exposure to PCBs. H. Engl. J. Med. 295:450, 1975. IB. Lawrence, C. PCB? and melanoma. N. Engl. J. Med. 296:108, 1977. 19. Brown. D.P., Jones, M. Mortality and industrial hygiene study of workers exposed to polychlorinated biphenyls. Arch. Environ. Health 36:120-129, 1981. 20. Berta22l, P.A., Zocchettl, C,, Guercilena, S., Foglle, M.D., Pesatorf, A., Riboldl, l. Mortality study of male and female workers exposed to PCBs. Int. Sympositai on Prev. of Occup. Cancer^ Helsinki, Finland, April, 1981. 21. Eighth Revision, International Classification of Diseases, Adapted for Use In the United States. U.S. Department of Health, Education, and Welfare, Publ1c Health Service, PHS Publication Ho. 1693. Washington: U.S. Govern ment Printing Office, 1977. 22. Monson, R.R. Analysis of relative survival and proportional mortality. Comput. Blomed. Ret. 7:325-332, 1974. 23. Ballar, J.C., Cderer, F. Significance factors for the ratio of a Poisson variable to Its expectation. Biometrics 20:639-543, 1954. 24. Krelss, K., Zadt, M.H.. Kimbrough, R.O., Needham. L.L.. Smrelc, A.L.. Jones. B.T. Association of blood pressure and polychlorinated biphenyl levtls. J.A.M.A. 245:2505-2509, 1981. 25. Bumgarner, J.E., Hammer, D.I., Colucci, A.V., Creason, J.P., Flnklea, J.F. Polychlorinated biphenyl residues in refuse workers. Research Triangle Park, North Carolina, National Institute of Environmental Health and Safety, Public Health Service, Department of Health, Conation, and wai- fere, 10 pp., 1973. HONS 004088 Judith A, ZjcSc/pij# ia Table 1 Follw-up Status of Polychlorinated Biphenyl Workers as of Decanter 31, 1977 Follow-up Status Number $tatus known 83 Verified alive 53 Verified deceased 30 Death certificate found 30 Death certificate net found 0 Status Unknown 1 Total 89 HONS 004089 Judith A. Zack/Pj^. is Table 2 person-years of Observation Contributed by Polychlorinated Biphenyl Workers by Age Age In Years Porson-years of Observation 20*24 11.4 25-29 63.8 30-34 142.6 35-39 222.5 40-44 233.2 45-49 325.3 50-54 294.5 55-59 207.6 60-64 134.0 65+ 115.2 Total 1800.1 HONS 004090 Judith A. Zick/Pagt 15 T*bl 3 Duration of Exposure to Polychlorinated Biphenyls by Vital Status Years of Exposure* Llvlng fn - 58) Vital Status Oeceased (N 30) Unknown (n 1) <1 20 S 1 1-3 20 12 0 3-5 6 4 0 >5 12 9 0 Total (n 89) 26 32 10 21 Average. Length of Exposure 3.2 yrs. 3,7 yrs. 0.7 yrs. 3.3 yrs. Lifttirae exposure prior to 1-1-66 HONS 004091 WH 1 lJ "> 1 Tibia 4 Obiarvad and Expactad Daathi Du* to Mi 11 (nant Naaplasas by Kara, fCO Itorttr Cohort l.C.O. NO. [eighth Ro*.) no-a Caaia of Doath Alt Malignant naoptiw Uhlta Katai 0 E INI* 4 Z.70 140 Nonwhlta Malei 0 E SMO* 4 1.74 ZZ7 140*140 110*110 Oaccat cavity 0 pharynx Olgoitlvn argiai I parltonaua 0 0.00 0 0.75 - 0 0.07 1 0.40 17Z 111, 150 110*114, 117*150 Llvtr Othar dlgaitlvn arfani 0 0.05 0 0,70 - 0 0.05 1 0.53 109 160.163 fciplratary lyitaa 3 0.94 319 1 0.19 149 ICZ. 161 160, 141 101.100 Lang Othar raiplratary oryaai Genitourinary argaai 1 0.09 0 0.05 0 o.zt 33/ - 1 0.11 10Z 0 0.04 1 0.Z3 435 zoo.too Lyapbatlc 4 bamtapalatlc tlnaa 0 O.ZO - 1 0.1Z 033 144*104, 190-100 Alt othar iltaa 1 0.36 Z7f 0 0.17 - . Total 0 E smo* 0 4.44 179 0 0.14 - 1 1.33 0 0.10 1 1.Z3 4 1.53 4 1.44 0 0.00 1 0.51 71 * 81 Z41 Z70 104 1 0.40 Z10 1 0.53 100 Ho SH8 mi ititlittcilly ilgnl/lcant (all p.valuni frcatar than 0.01) HONS 004092 act Honahtte Hnwhlte Nonwhlte Whitt Whitt Whitt Uonehlte White Tear o# llrth urn i*n 1*00 10*3 1*11 1*1* 1*07 1*00 Tahle S Celt Suaaarlet of Cancer Death* Amf Polychlorinated W phony I Wbrktri Tear of Flrjt Eipoiurt Ttar tf Death PC* Eipoiurt Duration (ao.) 1*41 its* 11 DS4 DCS S 1**1 1*43 1**1 1*01 1940 1*40 DM 19C3 1*M 1*77 19*4 1*S7 n 34 11 33 7* Death Certificate Caeie of Death (ICO#) Card float of colon (1*3*0) Card noaatoil*Prlaary ilte. kidney (lit.O) Carclntaa of lunt (KM) Carclntaa of right lung (1CM) Carclntaa ef loot (KM) Carclntaa ef lent (KM) ftiltlpl* nyeloaa (701.0) fetaitatlc carclnoaa. carctnoaatoili (1*9.0) HONS 004093 lJUU < IH it. i 4 k.1. -fS. ( Table C i.c.n. n. (El thill *.) HO-UI 410.413 300-409 414-4SO 460-519 SZ0-S77 no-too ObS*nrtd and xp*ct*d Deaths Du* td hon-oall^ant Caultl by fact, PCI Harttr Cohort c*t *r otath Hhlt* Haiti 0 E SHI hoouhlt* Haiti rt c sw 01i*aiai *f th* circula tory lyitaa 11 l.lt 161 5 4.3S US ArUr laid erotic heart lltettt 4 4.99 10 3 Z.ZO 13$ Ml *th*r drculatary lyitu 7 1.03 SIC* I Z.1S 93 rttiaaiai *f th* raiptratory lyitoa 0 0.73 . 1 9.S4 19$ lyitaa Eataroal caMi *f Otath All *th*r *00 i11yoot c*us*t 1 0.7S 0 1.43 133 - I 1.19 Itf 1 0.41 1 0.99 ZZZ 10$ 0 1.30 - Total 0 E SHI 16 11.17. 143 7* 7.19 97 9 3.91 ZZ6* 1 1.Z7 79 2 l.ZO 1 Z.30 167 4Z z Z.40 3 Tttal All caoiai, allynatt 1 Mo^allfiiant l* 13. S3 133 1Z 1.3$ )Z9 30 ZZ.M 131 p < 0.01 HONS 004094