Document OzY5e6DXaQgGJ9Gam45j75w8X

4- - Company work history records were used to classify employee exposures by work area assignment (Bond et al, 1985; 1986) as well as by potential for exposure to 11 chemical agents chosen because they had been shown to produce cancer of the liver or biliary passages under experimental conditions in animals (Chu et al, 1984; Haseman et al, 1984; NTP, 1985; Wilbourn et al, 1986). Visits to the Medical Department by the cases were reviewed by a nurse co-investigator (EAM) to ascertain a history of excessive alcohol use or hepatitis, as they are established risk factors for primary liver cancer (Falk, 1982). This exercise was of limited usefulness, however, owing to: (1) the unavailability of medical records for those subjects who terminated their employment prior to 1947 (N = 24) and (2) a lack of information concerning any post-employment illnesses among the workers. Risk ratios were computed adjusted for birthyear using the Mantel-Haenszel (1959) procedure. Analyses which additionally controlled for period of hire showed similar results to those which controlled only for birthyear and are not presented. Likewise, analyses of the primary liver cancers separate from the gall bladder/bile duct cancers did not reveal additional information and are not shown. Ninety five per cent test-based confidence intervals were calculated about the risk ratio estimates (Miettinen, 1976). RESULTS Analyses by work area assignments (Table I) showed the cases were signifi cantly less likely to have held assignments in electrochemicals or organic chemical R&S 100012 -5- production, but were more likely to have held assignments in office maintenance (RR = 3.6; 95% Cl = 1.4-9.1). A positive association with assignment to polyvinvlpolyvinvlidene chloride production did not reach statistical significance (RR = 2.0; 95% Cl = 0.9-4.6). There were no statistically significant trends apparent when analyses were made of duration of assignment within work areas; however, the odds ratio for an assignment of five or more years to polyvinyl-polyvinylidene chloride production was 3.7 (95% Cl = 0.9-14.6) based on the contribution of two cases. Assignment to polyvinyl-polyvinylidene chloride production areas was explored further in Figure 1 via a plot of the "attributable fraction" (Goldsmith et al, 1980) for each year during the period 1940-1980. The peak "attributable fraction" occurred-in 1952, a year in which four of the seven cases assigned to these areas were all employed, no two in the same plant, however. None of the chemical agent comparisons revealed statistically significant dif ferences (Table II). The highest risk ratio (RR = 2.2; 95% Cl = 0.9-5.7) was for pre sumed exposure to vinyl chloride based on the contribution of five cases. There were no statistically significant trends for analysis by duration of exposure to any of the 11 agents, although in many instances there were too few exposed cases to per mit meaningful conclusions. Likewise, there were no statistically significant trends apparent when analyses were made by estimated dose of exposure. R&S 100013 R&S 100014 -6- DISCUSSION The present investigation revealed a statistically significant positive associa tion with assignment to office maintenance, and some marginal associations with polvvinyl-polyvinylidene chloride production. The association with an assignment in office maintenance is curious, since this type of work is not generally considered hazardous. In fact, it was a common practice to assign to that department any work ers who were not considered medically fit to work in more strenuous jobs. Companv medical records were available to review for four of the five cases assigned to office maintenance, and revealed that two of the men had been hospital ized for chronic alcoholism suggesting that this finding may have resulted from confounding. High levels of vinyl chloride exposure have produced a specific hazard of angiosarcoma of the liver in some work forces (Doll, 1988). In the present study, five of the seven cases of liver and biliary tract cancer who held assignments in the polvvinyl-polyvinylidene work area were considered to have had the opportunity for exposure to vinyl chloride monomer. There was no evidence that any of the five cases experienced angiosarcoma, however, pathology reports and/or medical records were available to confirm the diagnosis for only two of them. Table III presents some descriptive information concerning these cases. By virtue of the time period in which they worked and the nature of their jobs, each of the men was con sidered to have had the opportunity for high levels of exposure to vinyl chloride monomer, with peak exposures probably exceeding 1000 ppm. Although two of the -7- cases had spent more than 20 years each in areas of potential vinyl chloride monomer exposure, the other three had very brief exposures on the order of one to several months. Of interest, none of the other chemical agents suspected a priori as potential risk factors was shown to be statistically significantly associated with liver or biliary tract cancer. It may be that some of the agents are weak carcinogens, but this study could not explore that hypothesis. An examination of the upper limits of the 95% confidence intervals about the risk ratios presented in Table II shows that the study apparently had sufficient power to rule-out modest increases in risk for several chemicals (i.e., carbon tetrachloride and ethylene dichloride), but only relatively large increases in risk could be excluded for others. Some misclassification of exposure may have occurred; however, the avail ability of industrial hygiene data from the distant past for many of the plants at this production site should have reduced this possibility considerably. If misclassification did occur, and was non-differential, the tendency would be to diminish the strength of the associations. R&S 100015 -8- ACKNOWLEDGEMENTS The authors gratefully acknowledge technical assistance from Tom Bradley, Wendy Dahar, Mike Dupuis, Stan Gorgacz, Harold Hoyle, Bruce Houtman, .Carl Mueller, Gordon Roush, Dan Schmidt, Belinda Scortichini, Tricia Stirrett, and Mike Strieter. They also thank Diana Diamond for help with preparation of the manuscript. R&S 100016 -9- REFERENCES Bond GG, Flores GG, Shellenberger RJ, Cartmill JB, Fishbeck WA, Cook RR (1986): Nested case-control study of lung cancer among chemical workers. American Journal of Epidemiol, 124; 1:53-66. Bond GG, McLaren EA, Cartmill JB, Wymer KT, Sobel W, Lipps TE, Cook RR (1987): Cause-specific mortality among male chemical workers. Am J of Industr Med 12:353-383. Bond GG, Shellenberger KJ, Flores GH, et al (1985): A case-control study of renal cancer mortality at a Texas chemical plant. Am J Industr Med 7:123-139. Chu KC^Cueto C, Ward JM (1984); Factors in the evaluation of 200 National Cancer Institute Bioassavs. J Toxicol Environ Filth 14:621-639. Doll SR (1988): Effects of exposure to vinyl chloride - An assessment of the evidence. Scand J Work Environ Health 14:61-78. Falk H (1982): Liver. In Schottenfeld D and Fraumeni JF (editors). Cancer Epidemiology and Prevention. Philadelphia: W. B. Saunders Company, pp. 668-682. Goldsmith OF, Smith AH, McMichael AJ (1980): A case-control study of prostate cancer within a cohort of rubber and tire workers. J Occup Med 22:533-541. R&S 100017 -10- Kupper LL, McMichael AJ, Spirtas R (1975): A hybrid epidemiologic study design useful in estimating relative risk. Journal of the American Statistical Assoication 70; 351:524-528,. Haseman JK, Crawford DD, Huff JE, Boorman GA, McConnell (1984): Results from 86 two-year carcinogenicity studies conducted by the National Toxicology Program. Journal of Tox and Environ Health 14:621-639. Miettinen OS (1976): Estimability and estimation in case referent studies. Am J Epidemiol 103:226-235. National Toxicology Program (NTP) (1985): NTP Technical Report on the toxicology and carcinogenesis studies of dichloromethane in F-344/N rats and B6C3F1 mice (Inhalation studies) NTP-TR-306 (board draft). Wilbourn J, Haroun L, Haseltine E, et al (1986): Response of experimental animals to human carcinogens: An analysis based upon the IARC Monographs programme. Carcinogenesis 7:1853-1863. R&S 100018 TABLE I AGE-ADJUSTED RISK RATIOS FOR ANALYSES BY MAJOR AND MINOR WORK AREAS; STUDY OF LIVER AND BILIARY TRACT CANCER AMONG CHEMICAL WORKERS, MIDLAND, MICHIGAN, 1940-82 Major/Minor Work Areas Exposure Frequencies (%) Cases (N = 44) Referents (N = 1888) RR 95% Cl R&S 100019 Administration 0.0 Manufacturing 68.2 Agricultural Chemicals 9.1 Herbicides 6.8 Insecticides 4.6 Inorganic Chemicals 47.7 Ammonia 0.0 Brine 6.8 Brominated Products 4.6 Calcium/Magnesium 9.1 Caustic 4.6 Cellulose Products 2.3 Electrochemicals 0.0 Metal Fabrication 22.7 Organic Chemicals 36.4 Acrylamide 0.0 Alkvl Benzenes 0.0 Chlorinated Benzenes 0.0 Dves 6.8 Fabricated Plastics 6.8 Glycols 0.0 Halogenated 4.6 Hydrocarbons Ion Exchange Resins 2.3 Latex 2.3 Olefins 4.6 Phenol Derivatives 6.8 Polvstvrene 6.8 Polyvinyl- 15.9 Polyvinylidene Chloride Unknown Manufacturing 0.0 Research 15.9 Service 65.9 Animal Handling 0.0 Boiler Shop 4.6 5.8 75.7 26.2 17.1 9.7 40.0 1.0 4.6 5.9 12.5 1.9 7.6 10.2 16.8 56.8 2.1 3.9 3.6 6.1 16.5 1.8 7.7 2.0 2.7 2.5 13.0 15.0 10.1 1.0 22.8 59.8 0.6 3.4 0.0- 1.5 0.7 0.4- 1.3 0.4 0.1- 1.0 0.5 0.2- 1.6 0.6 0.1- 2.4 1.1 0.6- 2.0 - 0.0- 8.4 0.9 0.3- 3.0 0.9 0.2- 3.7 0.7 0.2- 1.8 2.1 0.5- 9.5 0.4 0.1- 2.5 - 0.0- 0.8 1.1 0.6- 2.2 0.5 0.3- 0.9 - 0.0- 4.0 - 0.0- 2.2 - 0.0- 2.3 0.7 0.2- 2.3 0.6 0.2- 1.9 - 0.0- 4.7 0.4 0.1- 1.6 1.2 0.2- 8.7 0.8 0.1- 6.2 1.5 0.3- 6.7 0.4 0.1- 1.4 0.5 0.1- 2.0 2.0 0.9- 4.6 0.0- 8.4 0.8 0.3- 1.8 1.1 0.6- 2.0 - 0.0-14.0 1.0 0.2- 4.1 Continued on next page TABLE I CONTINUED AGE-ADJUSTED RISK RATIOS FOR ANALYSES BY MAJOR AND MINOR WORK AREAS; STUDY OF LIVER AND BILIARY TRACT CANCER AMONG CHEMICAL WORKERS, MIDLAND, MICHIGAN, 1940-82 R&S 100020 Major/Minor Work Areas Exposure Frequencies (%) Cases (N = 44) Referents (N = 1888) RR 95% Cl Service (continued) Construction Electric Shop Engineering Garage Lead Shop Lubrication Machine Shop Maintenance Material Handling Office Maintenance Paint Shop Pipe Shop Plant Protection Power Road and Yard Mtc. Shops-Steel & Instrument Waste Management Well Services 13.6 2.3 2.3 0.0 0.0 0.0 4.6 4.6 11.4 11.4 4.6 9.1 9.1 2.3 4.6 6.9 0.0 0.0 13.6 0.7 0.3- 1.7 2.8 0.9 0.1- 6.4 1.6 1.7 0.2-12.5 2.5 - 0.0- 3.4 0.3 - 0.0-28.0 0.4 - 0.0-21.0 4.2 0.9 0.2- 3.5 8.6 0.4 0.1- 1.6 8.1 1.4 0.5- 3.7 3.3 3.6 1.4- 9.1 7.9 0.6 0.1- 2.5 10.3 0.8 0.3- 2.3 5.6 1.1 0.4- 3.2 7.1 0.2 0.0- 1.3 2.0 2.2 0.5- 9.6 2.3 2.2 0.7- 7.5 1.2 - 0.0- 7.0 0.1 - 0.0-83.8 Workers may have been assigned to more than one work area during their employment and thus may be counted more than once in the Table. TABLE II AGE-ADJUSTED RISK RATIOS FOR ANALYSES BY SELECTED CHEMICAL AGENT EXPOSURES; STUDY OF LIVER AND BILIARY TRACT CANCER AMONG CHEMICAL WORKERS, MIDLAND, MICHIGAN, 1940-82 Agent Exposure Frequencies (%) Cases (N =44) Referents (N = 1888) RR 95% Cl . Carbon Tetrachloride 11.4 Chlorodibenzo-(p)-dioxins 2.3 Chloroform 4.6 Ethylene Dibromide 2.3 Ethylene Dichloride 6.8 Methylene Chloride 4.6 Perchloroethylene 13.6 Polychlorinated Biphenyls 0.0 1,1,2-Trichloroethane 0.0 2,4,6-Trichlorophenol 0.0 Vinyl Chloride 11.4 20.0 0.5 0.2- 1.4 9.1 0.2 0.4- 1.4 6.7 0.6 0.2- 2.7 7.3 0.4 0.1- 3.0 14.6 0.4 . 0.1- 1.3 8.9 0.8 0.2- 3.6 11.3 1.8 1.2 - 0.0- 7.0 0.5 - 0.0-16.8 0.9 - 0.0- 9.3 7.8 2.2 0.9- 5.8 Workers may have been exposed to more than one agent during their employment and thus may be counted more than once in the Table. R&S 100021 to i ooo TABU HI DESCRIPTIVE DATA ON FIVE CASES PRESUMED TO HAVE BEEN EXPOSED TO VINYL CHLORIDE MONOMER; STUDY OF LIVER AND BILIARY TRACT CANCER AMONG CHEMICAL WORKERS, MIDLAND, MICHIGAN, 1940-82 Case No. Year First Exposed Year Last Exposed Duration of Exposure (yrs; mo) Year of Death 1 1943 1943 0; <1 1960 2 1943 1943 0; 3 1964 3 1950 1970 20; 0 1976 4 1946 1967 20; 8 1980 5 1952 1952 0; 2 1972 Job Classification Best Diagnosis (Source) Assistant Operator Adenocarcinoma of common bile duct (DC) Janitor Carcinoma of liver (DC) Operator Hepatocellular carcinoma (PR) Operator Intrahepatic bile duct cancer (MR and PR) Handyman/Packager Cancer of liver (DC) DC = death certificate MR = medical record PR = pathology report 330001- S'SH Figure I. STUDY OF LIVER AND BILIARY TRACT CANCER AttributaDle Fraction for Assignment to Polyvinyl-Polyvinylidene Chloriae Areas in eacn Year During 1940-1980 R&S 100023 0.20 0 . 15 - Z G ---- lO T J ^ l 0.10 0.05 Ooo o <>ooO 0.00 r--r19 4 0 -r----- 1----------r-------1------ j------ r --- r 1 9 50 t~ --t------ 1------ t t 19 60 i------- p------- r------ 1------ r------- i-------1------ [ i------- 1" r i 19 70. r~ CALENDAR YEAR frZOOOt S'SH 1 9 80