Document k954QM9eyVJnD1mwG20dm7G9D

INTERNAL CORRESPONDENCE UNION CARBIDE CORPORATION 270 PARK AVENUE, NEW YORK. NY 10017 Tu O' vl&iilK O' A<-pri Dr. D. H. Glenn P. 0. Box 471 Texas City, Texas Dace Originating Oapt. Area Subject September 11, 1981 HS 4 EA - Toxicology 4th Floor Enclosed Is a rough draft of the Texas City Brain Tumor Case Control Study. This has been sent to our reviewers, Drs. Enterline and MacMahon today, Friday, September 11, 198land I expect to receive their comments the early part of next week. I would also appreciate your review of this paper with specific attention to the statements that are made regarding practices at the Texas City plant and creation of the chemical exposure dpeartmental dictionary. I look forward to talking with you next week. Very truly yours, SGA:lm Enclosure Susan G. Austin, Sc.D. Corporate Epidemiologist UCC 096816 THE RELATIONSHIP BETWEEN OCCUPATIONAL FACTORS ' AND BRAIN TUMORS INTRODUCTION IT In mid 1978 a duster of brain tumor oases (deaths) was identified among former employees of The Uhion Carbide Corporation (UCC) obeaical plant in Texas City, Texas. As a result of a formal employee request to The Occupational Safety and Health Administration (QSHA), the National Institute of Occupational Safety and Health (NIOSH) and UCC initiated a two-pronged .chit*. 6JAf *JLu$> investigation to determine (the occupational relatldnesa^oE this duster. The first prong of the investigation was a retrospective cohort mortality study of all employees who ever worked at the Texas City Plant and a comparison of their overall mortality experience ainoe 191*! with the mortality experience of the United States. The seoond prong of the NIOSH Investigation was a 7 case-control study to identify any exposure or work areas that were shared in common by the brain tumor cases. In addition to assisting NIOSH in the data collection requirements for their studies, UCC also initiated studies independently of NIOSH. The purpose of this report is to describe the results of an independent UCC sponsored case 0968)7 -2control study. PURPOSE The purpose of this study was to identify any occupational factors that could serve to distinguish the brain tumor cases from a randomly selected sample of all former UCC employees. Specifically, the study was intended to assess the likelihood that exposures to known or suspect carcinogens at the UCC Texas City plant oould have been related to the occurrence of the brain tumors among the population of employees who ever worked at the plant. A second purpose of the study was to attempt to replicate the results of the NIOSH case control study using an independently selected comparison population. This was considered an appropriate objective, since the validity of these studies often depends on the adequacy with which the comparison populations selected for study represent the underlying population from which the cases were drawn. Since both the UCC and NIOSH studies selected a random sample of the aggregate UCC Texas City employee population (approximately 9,000 individuals) to serve as "controls", both studies are subject to some degree of sampling error which could lead to spurious results. The chances that both studies will obtain the same spurious results are rather small; UCC 096818 -3therefore the results of the two analyses, taken together, should provide some assurance that a "real" association between soae chemical and the brain tumor cases will not be missed. METHODS The methods used in this study involved comparisons between the number or proportion - of brain tumor cases exposed to a particular chemical during employment at Texas City, with the number - or proportion - of non-brain tumor "controls" exposed to the same chemical during employment at Texas City. Carcinogens The five known or suspected carcinogens that were studied in this investigation include benzene, ethylene dichloride, ethylene oxide, diethyl sulfate and vinyl chloride. Although ethylene dichloride was a suspect carcinogen at the time this study was initiated, additional long term animal studies have been completed whieh have resulted in removal of this chemical from the suspect oarcinogen list.1 For this study, however, results for ethylene dichlorlde will be presented together with human carcinogens suspect UCC 096819 -U- Other Chemicals For the purpose of .replicating the results of the NIOSH case control study, the sane thirty (30) chemicals under investigation in that study were also included for study in this investigation. (Figure 1) these chemicals were selected by NIOSH because at least four brain tumor cases were found to have had the potential for exposure to the chemicals at some time during their employment at UCC Texas City. Description of Cases For the purpose of this study, a case was defined as any former UCC Texas City employee known to have had a primary brain tumor on the basis of autopsy information, pathology reports, clinical evidence in medioal records or death certificates. This definition of a "case" includes both malignant, benign and unspecified (mali&iancy) tumors. Case validation was performed by NIOSH and resulted in the identification of twenty-one (21) cases shown in Table 1. This table indicates the most accurate diagnosis available in this investigation as determined by NIOSH. The "source of confirmation" indicates the most valid source of information used in determining the specific diagnosis of the primary tumor. A code of "1" UCC 096820 .Figur 1 LISTING OF 30 CHEMICALS TO WHICH FOUR BRAIN TUMOR CASES WERE EXPOSED AT UCC TEXAS CITY Ethylene Acetaldehyde Acetic acid Acetone Butadiene C02 Diethanolamine Ethane Ethanol Ethylene glycol Hydrochloric acid Isopropanol Isopropyl acetate Methane Methanol Methyl ethyl ketone Methyl isobutyl ketone Monoethanolamine Propylene Sodium carbonate Sodium hydroxide Styrene Sulphuric acid Toluene Vinyl acetate Tergitols Mesityl oxide 4 Chlorine Trichloroethane Sodium sulphite UCC 096821 -5- : I, : Ui ' i: indicates that a tissue specimen, either from autopsy, biopsy, or surgery, was available and sent to pathologists at the Armed Forces Institute of Pathology (AFIP) for independent confirmation. Codes "2" and "3" indicate that no tissue specimens were available, but original copies of the pathology report from autopsy or surgery were available to NIOSH. A code of "4" indicates that no pathology report was available (either no surgery was performed or records had been destroyed), and the diagnosis listed represents that found in the hospital record. A code of "5" indicates that the death certificate diagnosis was the sole source of information regarding the presence and type of brain tumor. For the purpose of this analysis, oodes "1", "2" and "3" were considered by UCC as confirmed and codes "4" and "5" were considered unconfirmed. In all, this case series consisted of 21 cases: 17 classifiable as gliomas - or tumors arising from the glial cells, and 4 classifiable as meningiomas - or tumors arising from the cerebal lining (meninges). (Of th four meningiomas, three were benign tumors and one was malignant.) Of the seventeen (17) gliomas, thirteen were confirmed by available autopsy or pathology reports. UCC 096823 Selectlon of Controls -6- !TC\ u For purposes of comparison with Cases, two series of oontrol groups were selected from all former UCC Texas City employees whose deaths were known to the company. Decedents were used as controls for two reasons: 1) their causes of death were known and could be verified as non-brain tumor cases; and 2) all twenty-one (21) cases were also deceased. The two control groups differed In that Control Group I excluded employ es whose cause of death was attributable to any malignant neoplasm. Both control groups consisted of eighty (80) male employees randomly selected from 450 decedents known to the company in June of 1979* Exposure Determination A Exposure determinations were made on the basis of official employment records available at the Texas City plant. These records contained detailed job titles and plant departmental assignments for each employee from date of hire to date of termination at UCC Texas City. For each unique departmental code symbol, principal chemicals used or produced at any time in the history of the plant were identified and "linked" with that department (by UCC industrial hygienists). It was not possible to specify these associations by year. UCC 096824 -7- (: /. - /, _ vt "tj An employee was considered "exposed" to a given chemical if h ever worked in a department linked with that chemical. An employee was considered "unexposed" if he never worked in a department linked with that chemical. The "unknown" exposure designation was reserved for employees who were never known to have been exposed to a given chemical but who had worked in a department (e.g. maintenance) for which no specific chemicals could be listed. ANALYSES The proportion of cases exposed to a particular chemical was compared with * the proportion of controls exposed to the same chemical. For this comparison, employees whose exposure was "unknown" were excluded fhom analysis for both cases and controls.* x Because it is expected that a chemical carcinogen possibly capable of t.iT inducing brain tumors would be associated primarily with glial cell tumors, O' the proportion of glioma cases exposed to specific chemicals was also calculated for- comparison. In addition to overall analyses in which the comparison was between proportions of cases and controls ever exposed to specific chemicals at any time during their employment with UCC Texas City, a separate analysis was * "Analyses were also performed where (1) "unknown*'* ware considered "exposed" and (2) "unknowns" were considered "exposed". The results of these analyses are not rep rted in the paper. UCC 096825 -8performed in which the latent period of chemical carcinogenesis was taken into consideration. In this analysis, comparisons between cases and controls were restricted to employees whose first exposure to a particular chemical occurred a minimum of fifteen years prior to death. Because the nature of this study was primarily descriptive, no tests of nl statistical significance were performed routinely. When tests were used, the 2 Mantel Haenszel Chi statistic was calculated to determine whether the observed difference between two proportions could have been due to "chance" or random fluctuation if there were really no difference present in the underlying population. RESULTS Demographic and Occupational Characteristics The controls used in this study were selected for the purpose of representing the underlying population of males ever employed at Texas City. For this reason the controls were not matched to the cases on any demographic or occupational characteristics. Because the population from which the controls were selected were decedents whose deaths were known to company management, they likely underrepresent employees with brief periods of ucc 096826 employment*. A comparison of selected characteristics of cases and controls is shown in Table 2. Cases resembled controls quite closely on the characteristics year of hire, payroll status and race. A higher proportion of cases worked for less than 10 years than controls and terminated for reasons other than death, disability or retirement (voluntary quit, layoff, etc.). Cases were also found to be generally younger at hire than the controls. Zt is possible that these two factors are inter related, i.e. employees with brief periods of employment who terminate for reasons other than death or disability may be younger at hire than employees with longer periods of employment. Age at death was younger for cases than controls, reflecting the fact that the peak Incidence of brain tumors is in the fifth and sixth decade of life. Fever cases died before 1960 than controls and a greater proportion survived a minimum latent period of fifteen (IS) years following hire at the Texas City Plant. * Company identified deaths were known through the corporate employee benefits department and through locally published obituary notices routinely screened by the plant medical department. UCC 096827 I Table 2 COMPARISON OF CASES AND CONTROLS *?OR SELECTED CHARACTERISTICS CHARACTERISTIC Termination Reason Death Disability Retirement Other CASES NO. . 10 47.6 2 9.5 3 14.3 6 28.6 CONTROL I NO. t 38 47.5 16 20.0 19 23.8 7 8.8 Yrs. Service < 10 11-20 > 21 7 33.3 5 23.8 9 42.8 13 16.2 38 47.5 29 36.2 Yr. Of Hire 1940-1945 1946-1950 1951-1955 1956- 8 38.1 8 38.1 5 23.8 0 0.0 30 37.5 31 38.8 13 16.2 6 7.5 Aqe At Hire < 25 Yrs. 25-34 Yrs. 35 Yrs. payroll Type Status 5 10 6 23.8 47.6 28.6 Ever Hourly Never Hourly 21 100.0 0 0.0 Race White Other 18 85.7 3 14.3 Ace At Death < 50 Yrs. 50-69 Yrs. 70+ Yrs. 4 19.0 16 76.2 1 4.8 Yr. Of Death 1950-1959 1960-1969 1970 + 1 4.8 6 28.6 14 66.7 Latency < 15 Yrs. > 15 Yrs. Cause of Death Neoplasms Accidents Other TOTAL 2 9.5 19 90.5 21 100.0 0 0.0 0 0.0 0 0.0 21 100.0 14 17.5 27 33.8 39 48.8 72 90.0 8 10.0 63 78.8 17 21.3 24 30.0 46 57.5 10 12.5 7 8.8 28 35.0 45 56.2 20 25.0 60 75.0 18 22.5 36 45.0 10 12.5 16 20.0 80 100.0 CONTROL II NO. % 36 45.0 21 26.3 14 17.5 9 11.3 12 15.0 35 43.8 33 41.2 34 42.5 29 36.2 13 16.2 4 5.0 11 13.8 30 37.5 39 48.8 74 92.2 7 8.8 \ 66 14 82.5 17.5 18 22.5 52 65 0 10 12.5 12 15.0 17 21.2 51 63.8 18 22.5 62 77,5 0 0.0 52 65.0 13 16.3 15 18.7 SO 100.0 I- i UCC 096828 10 - This finding Is likely attributable to the higher proportion of causes of deaths among controls for which the median age at death is lover. With the possible exception of the differences related to age at hire all discrepancies between cases and controls appear to be attributable to differences in cause of death between Cases and Controls or to the higherproportion of cases terminating for reasons other than death, disability or retirement. These differences do not appear to be large enough or of sufficient significance to affect the comparability of exposure histories of cases and controls if a minimum latent period is taken into consideration. Exposure Characteristics Table 3 Indicates overall exposure determinations for cases and controls for each of the five suspect human carcinogens, benzene, diethyl sulfate, ethylene dichloride, ethylene oxide and vinyl chloride. It can be seen from this table that exposure determinations could not be made for 47 to 57 percent of the cases and for 55 to 70 percent of the controls in each group. As a result, the number of cases'and controls that could be used in the analysis were greatly reduced. This was due to the high proportion of UCC Texas City employees who are assigned to maintenance departments where plantvlde travel UCC 096829 TabW3 Exposure Status Of Cases And controls Fbr Five Chemicals Used Or Products At The 'Texas City Plant (1941-1977) CHEMICAL BENZENE Exposed N (%) CASES Unexposed N () Unknown N (%) OCNTHOL I Exposed Unexposed N " (%) N <%) Unknown N (%) CENTRE, II Exposed Unexposed N (%) N (%) 1 (4.8) 8 (38.1.) 12 (57.1) 12 (15.0) 19 (23.7) 49 (61.2) 5 ( 6.2) 19 (23.7) Unknown N () 56 (70.0) DIETHYL SULFATE 4 (19.0) 6 (28.6) 11 (52.4) 17 (21.2) 21 (26.2) 52 (65.0) 12 (15.0) 20 (25.0) 48 (60.0) ETHYLENE DICHLORITE 4 (19.0) 6 (28.6) 11 (52.4) 14 (17.5) 22 (27.5) 44 (55.0) 14 (17.5) 17 (21.2) 49 (61.2) ETHYLENE QXHE 2 (9.5) 7 (33.3) 12 (57.1) 9 (11.2) 25 (31.2) 46 (57.5) 11 (13.7) 20 (25.0) 49 (61.2) VINYL CHLORIEE 4 0.9.0) 7 (33.3) 10 (47.6) 12 (15.0) 22 (27.5) 46 (57.5) 13 (16.2) 18 (22.5) 49 (61.2) c o o o VO 0\ oo U) - 11 - makes exposure to all chemicals theoretically possible but technically unknown. In all subsequent tables, the "percentage exposed" is based on only those employees whose exposure status could be determined, and excludes those whose exposure status was unknown. Table HA compares exposures between cases and controls for each of the five suspect carcinogens. It can be seen that the proportion of cases exposed differs only slightly between all cases and all glioma cases. In addition the proportion of cases exposed is generally lower than or consistent with that for either Control Groups for each of these chemicals. Because the results of these analysis may be diluted due to the inclusion of salaried employees (who are at a lower risk of exposure to chemicals) in the control groups, analyses are shown on Table HB using only hourly controls. Again, there is little difference between the proportions of cases and the proportions of controls exposed to these chemicals. A more meaningful analysis is one which allows for some minimum latent period between initial exposure to a given chemical substance and the onset of disease or death. Tables 5A and 5B show the comparison of exposure frequencies among cases and controls for only those persons who were employed !;CC 096831 ' 1^' Table 4A Proportions of Cases and Controls Exposed to Five Chemicals at UCC Texas City ALL CASES Percent CHEMICAL Total Exposed BENZENE 9 11.1 DIETHYLSULFATE 10 40.0 ETHYLENE DI CHLORIDE 10 40.0 ETHYLENE OXIDE 9 22.2 VINYL CHLORIDE 11 36.4 Table 4B GLIOMAS Percent Total Exposed 111 11 CONTROL I Total Percent Exposed 8 9 9* 8 10 12.5 33.3 44.4 25.0 40.0 iiii iiiii i iiii iiiii ii ti i 31 38 36 34 34 38.7 44.7 38.9 26.5 35.3 CONTROL II Percent Total Exposed 24 20.8 32 37.5 31 45.2 31 35.5 31 41.9 Proportions of Cases and Hourly Controls Exposed to Five Chemicals at UCC Texas City CHEMICAL ALL CASES GLIOMAS J CONTROL I Percent Percent i Percent Total Exposed Total Exposed Total Exposed BENZENE 9 11.1 8 12.5 26 42.3 DIETHYLSUFLATE 10 ETHYLENE DI CHLORIDE 10 40.0 40.0 9 9 33.3 44.4 32 31 46.9 41.9 ETHYLENE OXIDE 9 22.2 8 25.0 29 31.0 VINYL CHLORIDE 11 36.4 10 40.0 29 37.9 CONTROL II percent Total Exposed 22 18.2 30 36.7 29 44.8 29 34.5 28 39. 3 UCC 096832 Table 5A Proporations of Cases and Controls Exposed 1 to Five chemicals at UCC Texas City at Least 15 Years Prior to Death CHEMICAL ALL CASES Percent Total Exposed BENZENE 9 11.1 DIETHYLSULFATE 9 33.3 ETHYLENE DI CHLORIDE 9 33.3 ETHYLENE OXIDE 8 12.5 VINYL CHLORIDE 10 30.0 ' ' "1 - GLIOMAS { CONTROL I Percent [ Percent Total Exposed i Total Exposed 8 12.5 | 30 30.0 | i 8 25.0 J 33 42.4 j i 8 37.5 ; 31 32.3 i i i 7 14.3 { 31 19.4 i i 9 33.3 } 33 30.3 i CONTROL 2 Percent Total Exposed 23 4.3 28 25.0 27 33.3 27 22.2 28 46.4 Table - 5B Proportions of Cases and Hourly Controls Exposed to Five Chemicals at UCC Texas City at Least 15 Years Prior to Death CHEMICAL ALL CASES Percent Total Exposed BENZENE DIETHYLSULFATE 9 9 11.1 33.3 ETHYLENE DICHLORIDE 9 33.3 ETHYLENE OXIDE 8 12.5 VINYL CHLORIDE 10 30.0 GLIOMAS Percent Total Exposed 8 12.5 ii ii 1|ii i CONTROL I Percent Total Exposed 26 30.8 8 25.0 i i 29 44.8 8 37.5 ii 27 33.3 7 14.3 ii 27 22.2 9 33.3 29 31.0 CONTROL II Percent Total Exposed 22 4.5 27 25.9 26 34.6 26 23.1 26 30.8 UCC 096833 ll-84\fPlF12 - Ui idl '^ vi 1J at UCC Texas City a minimum of fifteen years prior to death. For all five chemicals, the proportion of cases exposed were comparable with the proportion of controls exposed. This result was obtained even when salaried employees were removed from the control groups (Table 5B). Although no associations were detected between suspect carcinogenic chemical exposures and brain tumor cases, the possibility of some other chemical used or produced at the plant having an association with the brain tumor cases was also investigated. In this analysis, proportions of exposed cases and controls were compared for each chemical to which at least four of the brain tumor cases were exposed. This criteria resulted in the selection of 30 chemicals. Tables 6 and 7 compare exposures of cases with all controls and with hourly controls for each of the thirty chemicals. For approximately half of the chemicals listed, both "all cases" and "all glioma cases" were exposed less frequently than either Control Croup 1 or Control Group II. The actual number of chemicals for which this was true increased by two (2) when salaried employees were removed from the control groups. For five chemicals, - ethylene, isopropanol, vinyl acetate, chlorine and UCC 096834 Table 6 CTEhXCRLS1 Ethylene Acetaldehyde Acetic sold Acetone Butadiene co2 Dletheaolaelne Ethane Ethanol Ethylene tlyeol Hydrochloric add laopropenol 'Isopropyl acetate Methane Methanol Methyl ethyl ketone Methyl laobutyl ketone Monocthanolalne Propylene Sodiua carbonate Sodlua hydroxide Styrene Sulphuric acid Toluene Vinyl acetate Tarfltola Mealtyl oxide Chlorine Trlchloroethane Sodium sulphite mopobatxoh or casks jun> cot*ql ivu xxrosxD* by omacu. .-Ei 'ALL CASKS 'T&JOHAS Ml * * 9 8.9 8 87.5 CONTROL X M 36 72.2 ii If.4 10 40.0 34 44.1 n 26. 4 10 40.0 40 55.0 n 72.7 10 80.0 43 79.1 t 44.4 `7 42.9 31 67.7 10 70.0 9 77.8 36 63.9 10 40.0 9 44.4 33 51.5 37.5 7 28.6 32 50.0 9 33.3 9 25.0 35 37.1 11 54.5 10 50.0 38 50.0 11 54.5 10 60.0 36 61.1 11 54.5 10 80.0 39 46.2 11 38.4 10 40.0 40 47.5 8 f2.5 7 57.1 33 69.7 10 40.0 9 44.4 39 71.8 11 38.4 10 40.0 34 32.4 11 38.4 10 40.0 34 32.4 10 40.0 9 44.4 37 62.2 9 44.4 8 37.5 36 75.0 10 50.0 9 55.6 34 52.9 12 83.3 10 80.0 41 85.4 11 38.4 10 40.0 35 51.4 10 80.0 8 75.0 35 82.9 11 36.4 10 40.0 ,, 51.4 11 54.5 10 60.0 38 42.1 10 40.0 9 44.4 39 68.7 9 33.3 9 44.4 9 44.4 9 44.4 8 37.5 33 7 42.9 j 30 7 42.9 i 30 i 7 42.9 60.6 36.7 36.7 36.7 COHTAOL XX M9 27 70.4 31 51.6 36 58.3 37 81.1 24 70.8 30 70.0 24 50.0 24 - 32 25.0 37.5 36 58.3 31 71.0 33 48.5 36 50.0 25 60.0 33 66.7 31 41.9 31 41.9 32 62.5 26 61.5 30 66.7 36 91.7 30 46.7 25 80.0 31 48.4 34 50.0 32 62.5 25 54.0 22 40.9 23 43.5 22 40.0 1Cheniicals listed are those to which at least 4 cases could have boon exposed*. 2d - designate number of employee* whose exposure ststus oould be determined 3t - Refers to percent exposed UCC 096835 Table 7 CHEMICALS! Ethylene Acetaldehyde Acetic acid Acetone Butadiene C2 Diethanolamine Ethane Ethanol Ethylene flycol Hydrochloric acid leopropanol laopropyl acetate Methane Methanol Methyl ethyl ketone Methyl ieobucyl batons Monoethanolaelne Propylene Sodlus carbonate Sodlun hydroxide Styrene Sulphuric acid Toluene Vinyl ecetate Tergltola Mealtyl oxide Chlorine Trichlotoethaae Sodium sulphite PROPORTIONS OP CASES AMD BOORLX CONTROL "EVER EXPOSED' BY CHEMICAL S* "3* 1.9 10 50.0 11 36.4 11 72.7 9 44.4 10 70.0 10 40.0 37.5 9 33.3 11 54.5 11 54.5 11 54.5 11 36.4 62.5 10 40.0 11 36.4 11 36.4 10 40.0 9 44.4 10 50.0 12 3.3 11 36.4 10 0.0 11 36.4 11 54.5 10 40.0 9 33.3 9 44.4 9 44.4 9 '44.4 HOURLY GLIOMAS CONTROL X 1 H 7.5 1111 r 31 i9 44.4 29 1 0.6 51.7 10 10 40.0 0.0 111111 34 37 5. 6.5 7 42.9 1>| 26 9 9 77. 44.4 1f11l 31 2S 76.9 74.2 57.1 7 29.6 11 27 59.3 10 25.0 50.0 1 111 30 33 43.3 54.5 10 60.0 1 31 67.7 10 60.0 33 1 10 40.0 34 44.5 50.0 7 57.1 1 2 2.1 9 44.4 34 79.4 10 40.0 29 34.5 10 40.0 29 34.5 9 44.4 32 -4 69. 37.5 30 83.3 9 55.6 29 62.1 10 0.0 3S 91.4 10 40.0 30 56.7 75.0 29 9.7 10 40.0 30 56.7 10 60.0 33 45.5 9 44.4 33 72.7 37.5 2 67.9 7 42.9 25 40.0 7 7 42.9 42.9 1111 25 25 40.0 40.0 SOURLY CONTROL II N 25 72.0 29 51.7 33 57.6 34 2.4 23 73.9 2 71.4 23 52.2 23 26.1 30 36.7 33 57.6 2* 71.4 30 46.7 33 4*.5 24 62.5 31 67.7 28 39.3 28 39.3 30 63.3 24 62.5 28 67.9 33 93.9 27 44.4 23 2.6 28 46.4 31 48.4 30 63.3 23 56.5 21 42.9 22 45.5 21 42.9 IChemicals listed ere those to which at least 4 cases could have bean 'exposed*. 2N - Designate number of employees whose exposure status oould be determined ^t - Refers to percent exposed UCC 096836 [ Table 8 PROPORTIONS OP CASES AMD CONTROLS "EVER EXPOSED' 15 YEARS OR MORE PRIOR TO DEATH BY OUMICAL CHEMICALS1 Ethylene Acetaldehyde Acetic acid Acetone Butadiene C2 Diethanolamine Ethane Ethanol Ethylene glycol Hydrochloric acid leopropanol leopropyl acetate Methane Methanol Methyl ethyl ketone Methyl lsobutyl ketone Honoethanolaalna Propylene Sodium carbonate Sodlua hydroxide Styrene Sulphuric add Toluene Vinyl acetate Tergltola Mealtyl oxide Chlorine Trlchloroethane Sodiim sulphite All* CASES m2 88.9 22.2 10 20.0 10 70.0 9 44.4 9 55.6 9 33.3 8 37.5 8 25.0 10 30.0 10 50.0 10 40.0 10 20.0 8 62.5 9 33.3 10 30.0 10 20.0 9 33.3 9 33.3 9 33.3 11 81.8 10 20.0 10 80.0 10 20.0 10 50.0 9 33.3 9 33.3 9 44.4 9 44.4 9 44.4 gliomas M CONTROL I Nt 87.5 34 55.9 8 25.0 33 30.3 9 22.2 35 43.7 9 77.8 37 73.0 7 42.9 32 59.4 8 62.5' 35 42.9 8 37.5 31 38.7 7 28.6 32 37.5 7 14.3 9 33.3 32 31.3 33 39.4 9 55.6 35 48.6 9 44.4 35 37.1 9 22.2 35 42.9 7 57.1 33 54.5 8 37.5 33 66.7 9 33.3 33 27.3 9 22.2 33 27.3 8 37.5 33 48.5 8 37.5 34 61.8 8 37.5 35 40.0 9 77,8 37 81.1 9 22.2 33 42.4 8 75.0 34 70.6 9 22.2 33 42.4 9 55.6 33 36.4 8 37.5 35 31.4 8 37.5 32 50.0 7 42.9 31 23.6 7 42.9 31 29.0 7 42.9 1 31 23.6 CONTROL II N% 25 52.0 29 44.8 31 41.9 32 71.9 24 58.3 28 57.1 24 37.5 24 16.7 28 25.0 31 48.4 28 57.1 29 37.9 31 41.9 25 52.0 28 57.1 27 29.6 27 29.6 28 46.4 25 48.0 28 57.1 32 78.1 27 29.6 25 64.0 27 33.3 30 36.7 29 48.3 24 41.7 23 26.1 24 29.2 23 35.3 iQiemicals listed are those to which at least 4 eases could have been exposed" N - designate niabtr of rapleyiti whose exposure atatua oould be determined 31 - Rafara to paroant axpoaad UCC 096837 sodium, sulfite, cases were exposed more frequently than controls. When salaried employees were removed from the control groups, cases were exposed more frequently than controls to only three chemicals: ethylene, isopropanol and vinyl acetate. Tables 8 and 9 show the comparison of exposure frequencies among cases and controls for those persons who were employed at UCC Texas City a minimum of fifteen years prior to death. For fifteen of the thirty chemicals listed, both "all cases" and "gliomas" were exposed less frequently than either of the control groups. The same result was found when cases were compared with only hourly controls. For nine chemicals, ethylene, isopropanol, methane, methyl ethyl ketone, sulphuric acid, vinyl acetate, chlorine, tricbloroethane and sodium sulfite, cases were exposed more frequently than either Control Group I or Control Group II. When the comparison was restricted to hourly controls, only methane was dropped from this list. A comparison of the proportion of gliomas and non-cancer hourly controls exposed to these remaining eight chemicals is shown in Table 10. Due to the small differences between these proportions and the small numbers on which UCC 096838 Table 9 PKOPOKTIOHS OP CASES AND HOURLY COMTROLS EVERT EXPOSED* 15 TEAM OR MORE PRIOR TO DEATH BY CHEMICAL CHEMICALS1 Ethylene Acetaldehyde Acetic acid Acetone Butadiene 02 Diethanolamine Ethane Ethanol Ethylene slycol Hydrochloric acid laopropanol ALL CASES M2 *3 18.9 9 22.2 ID 20.0 10 70.0 9 44.4 9 55.6 9 33.3 1 37.5 25.0 10 30.0 10 50.0 10 40.0 GLIOMAS M% 87.5 i 9 25.0 9 22.2 9 77.8 7 42.9 8 62.5 9 37.5 7 28.6 7 14.3 9 33.3 9 55.6 9 44.4 HOURLY C0HTH0L I H 30 60.0 29 34.5 31 49.4 33 76.8 28 64.3 31 46.4 27 40.7 28 42.9 26 35.7 29 41.4 31 51.6 31 38.7 HOURLY CONTROL II M 24 54.2 27 44.4 29 41.4 30 73.3 23 60.9 26 57.7 23 39.1 23 17.4 27 25.9 29 48.3 26 57.7 27 37.0 Isopropyl acetate Methane Methanol Methyl ethyl ketone Methyl Isobutyl ketone Monoethaaolaalne Propylene Sodlix carbonate Sodlus hydroxide Styrene Sulphuric acid 10 20.0 8 62.5 9 33.3 10 30.0 10 20.0 9 33.3 9 33.3 9 33.3 11 81.8 10 20.0 10 80.0 9 22.2 7 57.1 9 37.5 9 33.3 9 22.2 8 37.5 e 8 37.5 8 37.5 9 77.8 9 22.2 8 75.0 31 45.2 29 62.1 29 72.4 29 27.6 29 27.6 29 51.7 30 66.7 31 45.2 33 84.8 29 44.8 30 73.3 29 41.4 24 54.2 27 59.3 25 28.0 25 28.0 27 48.1 24 50.0 26 57.7 30 80.0 25 28.0 24 66.7 Toluene Vinyl acetate Tergltole Meeltyl oxide Chlorine Tricbloroethane Sodli* sulphite 10 20.0 10 50.0 9 33.3 9 33.3 9 44.4 9 44.4 44.4 9 22.2 9 55.6 8 37.5 8 37.5 7 42.9 7 42.9 7 42.9 29 44.8 29 37.9 31 54.8 28 53.6 27 25.9 27 29.6 27 25.9 25 32.0 28 35.7 28 50.0 23 43.5 22 27.3 23 30.4 22 27.3 ^ Otemicals listed srs thoss to which at least 4 cases oould have been exposed* 2 n - Designate nixeber of employees whose exposes status oould be deterwin d 2 I - Refers to peroeat exposed UCC 096839 Table 10 PERCENT EXPOSED BETWEEN GLIOMAS AND HOURLY NON-CANCER CONTROLS FOR EIGHT CHEMICALS 15 YEAR LATENCY ANALYSIS Chemical Ethylene Isopropanol Methyl ethyl ketone Sulphuric acid Vinyl acetate Chlorine Trichloroethane Sodium sulphite GLIOMAS Percent Total Exposed 8 87.5 9 44.4 9 33.3 8 75.0 9 55.6 7 42.9 7 42.9 7 42.9 CONTROL GROUP I Percent Total Exposed 30 60.0 31 38.7 29 27.6 30 73.3 29 37.9 27 25.9 27 29.6 27 25.9 UCC 096840 -m - these proportions are based, none of the differences are statistically significant. A separate analysis was performed in which an employee was assumed to have been exposed to all chemicals if he had ever worked in a department for which no specific chemicals could be determined ("unknown"). Hie results of this anang both Cases and Oontrols analysis (not shown) indicated higher exposure frequencies/^ for all chemicals but again no statistically significant differences between cases and controls were found. DISCUSSION The results of this study do not identify any specific associations between brain tuners and exposure to used five known or suspect carcinogens^at the UCC Texas City plant. This conclusion is based on the finding that employees who did not have malignant brain tumors were exposed to these carcinogens as frequently as employees who had primary brain tumors. This same result was found when a minimum fifteen year latent period was required between the date of first exposure and the date of death. The 'examination of an additional thirty (30) chemicals resulted in identification of eight (8) for which exposure frequencies among cases were UCC 096841 * L - 15 higher than among controls. With the exception of one of these eight, ethylene, the differences in exposure frequencies were less than twenty percent (20^) and none of the differences achieved statistical significance. For six of these chemicals, ethylene, isopropanol, sulphuric acid, vinyl acetate, chlorine and trichloroethane, carcinogenic potential has been investigated to some extent. Of these six, only chorine and trichloroethane have yielded positive findings. For chlorine, several epidemiologic studies have reported a link between chlorinated drinking water and cancer of the rectum, colon and bladder. For trichloroethane, one of the two isomers (112) has shown positive results, only in mice (not in rats). The other isomer (111) has shown no evidence of carcinogenicity in mice or rats and this is the isomer that has been handled almost exclusively at the Texas City plant. ,* For the other two chemicals, methyl ethyl ketone and sodium sulfite, no toxicological or epidemiological studies have been reported to date. One limitation of this study is that the control groups were selected from former employees whose deaths were known to the company. As a result, former UCC- Texas City employees who voluntarily terminated employment before retirement, or were laid off were underrepresented among controls. It can be T - 16 *,k r M'i. i .. V-ji Vm. Wy v u U argued that this restriction may have biased the study results since those employees not represented among the controls would have had shorter lengths of employment in general and consequently less opportunity for exposure. However, there is no reason to suspect that employees who continue working with a company will be less affected by such exposures than employees who terminate. In addition, the observation that a high percentage of the cases had relatively few (less than ten) years of company service, draws attention to the fact that employment and potential exposures outside of UCC Texas City has not been considered in this investigation. A second limitation of this study is the problem of accurately determining exposures among the Cases and Controls. Because of the nature of the Texas City plant (and all chemical plants in general) which requires a high percentage of the work force to be employed in maintenance activities, worker mobility is extremely high and very difficult to trace from day to day. As a result of this constraint, exposures to specific chemicals could be determined for only approximately half of the employees. For this reason and because of the extremely small numbers involved, the results of this study must be interpreted cautiously. However, to the extent UCC 096843 17 that enployee exposures were known, no evidence of a significant association between exposures to specific chemicals and employment at Texas City were found. UCC 096844 t t REFERENCES 1. Carcinogenic Factors, Report No. 2, Regulatory Technical Information Center, April 1979. 2. Fleiss, J.L. - Statistical Methods For Rates and Proportions, Wiley 1973, P. 18 UCC 096845 fc 6>/ \ J .70 "j '--I-------------1--------------- 1-------------1------------------ 1-- mo-Tl -7F13 72-74 73-75 74-7<, ucc 096846 SKRs BY LENGTH OF EKPIjOYHENT TEXAS CITY COHOST All HN Pancreas Respiratory Kidney Brain ?IM Respiratory Disease <-15 Years t SKR 83 2 75 13 79 00 2 68 10 81 > 15 Years 1 SKR 71 7 169 8 64 4 202 7 273 ' 6 32 Cause Brain FRQK KMWR REPORT al 10 95 ` SKRs 10-20 131 >20 304 UCC 096847 PROPORTIONS OF UCC BRAIN TUMOR DEATHS AND EMPLOYEES AMONG GALVESTON COUNTY RESIDENTS 1956-1977 PRIMARY BRAIN CANCER DEATHS NO. AT RISK ESTIMATED GALVESTON COUNTY A7 35,988* UCC 10 3700* PROPORTION FROM UCC 21% 10% i C o\ 00 oo OBSERVED AND EXPECTED DEATHS IN A COHORT OP 5113 WHITE MALE HOURLY EMPLOYEES (TEXAS CITY 1941-1977) CAUSE OP DEATH All Causes All Malignant Neoplasms MK-Digestive System Large Intestine Pancreas KN-Respiratory system Lung MN-Skim MN-Genito Urinary System Kidney MN-Lyaphopoeitic System Leukemia MN-Brain & Other CNS All Benign Neoplasms Allergic Metab. and Nutr. Diseases All Circulatory Diseases All Respiratory Diseases' All Digestive Diseases All Genito-Urinary Diseases All External Causes 035. 49 122 32 9 9 44 43 4 9 5 13 6 10 8 9 296 23 18 9 134 EXP. 769.0 146.3 38.6 11.9 7.8 50-7 47.8 3.2 14.2 3.9 16.6 6.3 6.1 2.4 12.1 357.3 37.9 44.7 10.2 115.7 SHR 0.84* .83 .83 .75 1.14 .87 .90 1.22 .63 1.27 .78 .94 1.64 3.24* .74 .83* .61* .40* .88 1.16 ^Indicates statistical significance at ,05 level UCC 096849 OBSERVED AND EXPECTED DEATHS XN A COHORT OF 6585 WHITE KALES (TEXAS CITY 1941-1977) CAUSE OF DEATH All Causes All Malignant Neoplasms KN-Digestive System Large Intestine Pancreas MN-Respiratory System Lung KN-Skin Ks-Genito Urinary System Kidney KN-Lyicphopoeitic System Leukemia MN-Brain & Other CHS All Benign Neoplasms Allergic Metab- and Natr. Diseases All Circulatory Diseases All Respiratory Diseases All Digestive Diseases All Gen.ito-Urinary Diseases All External Causes OBS. 728 138 37 11 10 48 46 5 9 5 16 6 10 8 10 334 24 20 9 155 EXP. 898.1 169.4 44.4 13.8 9.0 58.4 55.1 3.9 16.3 4.5 19.6 7.5 7.2 2.9 14.1 410.8 43.7 52.4 n.9 143.0 SKR 0.81* 8.81* 0.83 0.80 1.11 0.82 0.83 1.28 0.55 1.10 0.81 0.80 1.39 2.76* 0.71 0.81* 0.55* 0.38* 0.75 1.08 indicates statistical significance at .05 level UCC 096850 I UCC TEXAS CITY EXPOSURE DATA Benzene Diethyl Sulfate Ethylene Ethylene Dichloride Ethylene Oxide Polyethylene Vinyl Chloride Exposed Cases 9% (11) 271 (11) 73% (ID 27% (ID 101 (10) 30% (10) .4 25% (12) Exposed Control l 28% 39% 59% 33% 20% 10% 30% Exposed Control 2 10% 30% 53% 38% 30% 6% 26% UCC 096851