ORIGINAL ARTICLE
Surveillance for Angiosarcoma of the Liver Among Vinyl Chloride Workers James J. Collins, PhD, Brenda Jammer, BS, Frank M. Sladeczek, MD, Catherine M. Bodnar, MD, and Sergio S. Salomon, MD
Objective: We report the results of our angiosarcoma of the liver (ASL) registry to assess the occurrence, the impact of exposures to vinyl chloride, and to quantify latency. Methods: We examined more than 73,000 death certificates of North American workers employed between 1940 and 2008. Results: We found 13 deaths of ASL among workers with vinyl chloride exposure. All 13 occurred at single plant among workers with high vinyl chloride exposure. The mean latency after first exposure was 36.5 years ranging from 24 to 56 years. No ASL deaths occurred among workers with vinyl chloride exposures after 1974, when exposures were reduced. Conclusions: We may have seen the last case of ASL among workers exposed to vinyl chloride. Nevertheless, given the long latency of this cancer, continued surveillance seems prudent.
I
n the early 1970s, an experimental study indicated that exposure to vinyl chloride may cause cancer.1 Soon after, the Goodrich Chemical Company reported that three of its workers employed in the manufacturing of vinyl chloride resins had died of rare tumor, angiosarcoma of the liver (ASL).2 Workers at this plant were part of a North American industry-wide study of workers exposed to vinyl chloride, which reported initial results in 1974, including an increased risk of ASL.3 An experimental study in rats also reported an increase in this rare cancer after exposure.4 Given the findings from these studies, steps were taken to reduce vinyl chloride exposure across the industry.5–7 Several epidemiology studies were begun,8 and surveillance for this rare cancer was undertaken by both government and industry.9–11 Today, the two largest epidemiology studies on workers exposed to vinyl chloride are the North American and the European industry-wide studies. The North American study has been updated three times.12–15 The most recent update of this study found 48 angiosarcomas of the liver among 80 liver cancer deaths.15 The findings of the North American study are very similar to a European industry-wide study of vinyl chloride monomer workers, which found 37 angiosarcomas among 53 deaths from liver cancer.16 These studies and registries indicate that the risk of this rare cancer associated with vinyl chloride exposure extended across regions and might have a long latent period after first exposure extending beyond 35 years.10,17 The International Agency for Research on Cancer currently classifies vinyl chloride as carcinogenetic to humans based on sufficient evidence of increased risk of angiosarcomas of the liver and hepatocellular carcinomas.18 The Dow Chemical Company plants of Midland, Plaquemine, Sarnia, Freeport, South Charleston, and Texas City are included in the North American industry-wide study. The South Charleston and Texas City plants were originally part of Union Carbide until a merger with Dow in 2001. The company offers periodic medical examinations to its workers. A company disease registry for ASL was established in 1974.19 Individual epidemiology studies of cancer risk from vinyl chloride exposure have also been undertaken at some of From The Dow Chemical Company, Midland, Mich. Source of funding: The Dow Chemical Company. Conflicts of interest: None. Address correspondence to: James J. Collins, PhD, The Dow Chemical Company, 1803 Building, Midland, MI 48674 ([email protected]). C 2014 by American College of Occupational and Environmental Copyright Medicine DOI: 10.1097/JOM.0000000000000247
these locations.7,20–22 In addition, plant-wide mortality studies have also been done at sites where vinyl chloride monomer exposure was possible.23–30 We report the results of our most recent update of this ASL registry to assess the occurrence of new cases of this liver cancer, to assess exposures and latency periods of the occurrence of all cases, and to determine whether continued surveillance is needed.
METHODS Angiosarcoma of the liver is a rare cancer making up less than 1% of the primary hepatic tumors in the general population.31,32 It is an aggressive malignancy that is rapidly fatal and difficult to diagnose without liver biopsy.32 The Dow Epidemiology Department has established a database to collect employee demographic, vitals status, death certificates, and work history, and address data on all full-time US employees who worked more than 3 days since January 1, 1940. Currently, we have 189,572 current or former North American workers in this system. Of these, 74,759 are deceased and we have death certificates on 73,925 of the decedents (98.8%). The sources of data on vital status and deaths include internal pension information and external sources, including the National Death Index, states’ vital statistics offices, the Social Security Administration, credit bureaus, and state motor vehicle departments. In our registry, cases of angiosarcoma of liver were identified from death certificates with histology confirmation prior to 1990. These cases are also recorded in the angiosarcoma liver registry for vinyl chloride workers by the Association of Plastic Manufacturers.10 After 1990, we relied primarily on death certificates to identify new deaths from this cancer because obtaining pathology reports has become more difficult. For the United States, we searched all death certificates from January 1, 1940, to December 31, 2011, for “angiosarcoma of the liver,” “hemangiosarcoma,” or “angiosarcoma” as an underlying, contributing, or condition present at death. We also examined death certificate codes under versions of the International Classification of Diseases (ICD) where ASL cases may be coded to assure that we did not miss any cases in our initial review (ICD-10: C22-C24, C49, C78.7). For our two Canadian plants, we included all workers employed for 12 months between 1950 and 1996 and searched the Canadian Mortality Data Base from 1950 to 1996.23 As mentioned previously, there was an effort to reduce vinyl chloride monomer exposures across the North America industry in 1974 and there is evidence that this reduction was successful.5–7,21 These reductions were from several hundred parts per million (ppm) to 5 ppm or less. Thus, vinyl chloride exposures pre- and post-1974 were very different and may be important for assessing ASL risk. We identified workers employed at any of the six aforementioned plants that were included in the North American industry-wide study.15 That study included workers who worked for at least 1 year in a job where there was exposure to vinyl chloride between January 1, 1942, and December 31, 1972. In our assessment, all workers with potential exposure to vinyl chloride were included, regardless of duration of possible exposure. This would include workers exposed less than 1 year, workers with intermittent exposures, and exposures that occurred before 1942 and after 1972. We also included workers who worked in maintenance jobs with plant-wide responsibilities as
JOEM r Volume 56, Number 11, November 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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TABLE 1. Potential Deaths From Angiosarcoma of the Liver Identified From the Dow Angiosarcoma of the Liver Registry
Site Plants w/o VCM exposure Plants with VCM exposure 1. Midland 2. South Charleston 3. All other plants Total
Potential Deaths From Angiosarcoma
Angiosarcoma of the Liver Listed on Death Certificate or Histology Report
Job Listed on Work History With Potential Vinyl Chloride Exposure
Potential Exposure and Angiosarcoma of the Liver Diagnosis
Included in North American Industry Wide Study
Identified as Angiosarcoma of the Liver in North American Industry-wide Study
1 19 4 15 0 20
1 14 1 13 0 15*
0 15 0 15 0 15†
0 13 0 13 0 13
NA 13 NA 13 NA 13
NA 11 NA 11 NA 11‡
*The five deaths that were not angiosarcoma of the liver were deaths from angiosarcoma of the heart (1), angiosarcoma of the spine (1), angiosarcoma of the knee (1), angiosarcoma of the scalp (1), and angiosarcoma of the lung (1). †Five workers had no indication of exposure to vinyl chloride on their Dow work history. Nevertheless, two workers had general maintenance jobs with potential exposure. We classified these two workers as exposed. ‡The two deaths were not included in the most recent North American Industry-wide study. One case of angiosarcoma of the liver occurred after the end date of the study and the other had liver failure as the cause of death but additional information indicated it was angiosarcoma of the liver. NA, not applicable; VCM, vinyl chloride monomer.
6
having potential exposure. Review and oversight were provided by a human subjects review board in Midland, Michigan.
5
RESULTS
DISCUSSION Establishing an ASL disease registry for workforces with potential exposure to vinyl chloride is useful because this cancer is rare in humans and has been associated with only a few workplace exposures including vinyl chloride, and the latency period seems to 1208
4 Number
We identified 20 deaths with “angiosarcoma of liver,” “hemangiosarcoma,” or “angiosarcoma” from any our death certificates or from additional information from histology reports as shown in Table 1. Only 15 of these deaths were ASL. The other 5 deaths were angiosarcoma at sites other than the liver. Fifteen of the 20 deaths also had potential exposure to vinyl chloride according to their work histories and all 15 were located at the South Charleston plant. Thirteen deaths, all at the South Charleston plant, had both a diagnosis of ASL and potential exposure to vinyl chloride. All 13 workers with the diagnosis were included in the North American industrywide study. The exposure estimates developed for that plant for the study indicated that all decedents had high exposures to vinyl chloride. Eleven of the 13 were identified as angiosarcoma of liver in the North American industry-wide vinyl chloride worker study.15,33 One of the two deaths not included occurred after the North American study end date and the other that was listed as a “liver failure” on the death certificate. Additional histology information indicated that this case was an ASL. We did observe two deaths from ASL that occurred among workers without exposure to vinyl chloride according to their work history. One worker was employed at a plant with no vinyl chloride exposure and the other worked at a plant with vinyl chloride but in a job and department with no potential for exposure. Figure 1 presents the deaths for ASL by decade of death. Ten of the 13 deaths occurred in the 1970s and 1980s. The decades of the 1960s, 1990s, and the period 2000–2011 each reported a single death from this disease with the first death reported in 1968 and the latest death occurring in 2002. We also examined year of first exposure for the ASL cases. Twelve of the 13 workers were first exposed to vinyl chloride between the years 1940 and 1949. The remaining worker was first exposed in 1965. The mean number of years between first exposure and death was 36.5 years ranging from 24 to 56 years.
3 2 1 0 1960's
1970's
1980's
1990's
2000's
FIGURE 1. Deaths from angiosarcoma of the liver among workers with potential vinyl chloride exposure by decade of death.
be very long. We have been successful in establishing our registry of angiosarcoma of liver deaths because we routinely collect demographics, company work history, vital status of all former workers, and death certificates for all deceased workers for our US workforce. For our Canadian sites, we do periodic plant-wide assessments but have limited access to the death certificates to comply with Canadian confidentiality laws. In this registry, we identified 15 cases of ASL. Thirteen of these cases were among workers at a single plant all with high vinyl chloride exposure occurring before 1974. We found no cases of ASL among workers with vinyl chloride exposures after 1974. The risk of ASL has been related to very high exposures to vinyl chloride.16 The fact that all of the deaths related to ASL occurred at a single plant could indicate that exposures were higher at this location than at the other locations. The limited information we have on historical exposures at these plants in the registry supports this conclusion.7,15,21 We also identified two deaths of ASL among workers who did not have Dow workplace exposure to vinyl chloride. Angiosarcoma of the liver has other environmental causes other than vinyl chloride monomer and some cases are idiopathic. These two deaths out of the more 70,000 deaths we reviewed are consistent with background rates of ASL reported for the United States.31
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JOEM r Volume 56, Number 11, November 2014
There are some limitations to this study. First, the diagnosis for ASL has not been verified by histology reports in recent years but relies solely on causes recorded on the death certificate. The death certificate is an unreliable source of information about the histology of liver cancer.8,15 It is possible that some angiosarcomas of the liver were not reported in our registry but were recorded simply as liver cancer or liver failure on the death certificate. We observed an example of this type of underreporting of an ASL case in the North American industry-wide study where the death certificate listed “liver failure” as the underlying cause of death. Nevertheless, given the amount of public attention the association between vinyl chloride exposure and angiosarcoma of liver has received, we think it unlikely that the number of cases missed would be significant in either this study or the North American industry-wide study. We also observed three angiosarcomas at sites other than the liver among the South Charleston plant workers. Like ASL, these are relatively rare tumors. Mundt and colleagues15 observed an excess of soft tissues sarcomas in general among the North American vinyl chloride workers including angiosarcomas at other sites. Because of coding conventions for causes of death, many of these soft tissue tumors are grouped with other cancers at the same anatomical site, making it difficult to analyze them as a group. Another limitation of our registry is that the exposure characterization to vinyl chloride, especially exposures in the early years, is limited by lack of monitoring information, making it difficult to compare plants by exposure levels. All of the cases in our registry were first exposed to vinyl chloride before 1974, with all but one of the cases exposed before 1950. The most recent death occurred in 2002, and no additional cases have been observed in the past 7 years of observation. The mean latency period for ASL after first vinyl chloride exposure was 36.5 years in our registry. We have seen no deaths from ASL among workers first exposed after 1974 at several plants when exposures to vinyl chloride were much lower. We may have seen the last case of ASL among our workers exposed to vinyl chloride. Although our findings are based on a single company’s experience, we find no evidence of increased risk of ASL among workers with low vinyl chloride exposure. Nevertheless, given the long latency of this cancer, continued surveillance seems prudent.
REFERENCES 1. Viola PL, Bigotti A, Caputo A. Oncogenic response of rat skin, lungs and bones to vinyl chloride. Cancer Res. 1971;31:516–519. 2. Creech JL, Johnson MN. Angiosarcoma of liver in the manufacture of polyvinyl chloride. J Occup Med. 1974;16:150–151. 3. Tabershaw IR, Gaffey WR. Mortality study of workers in the manufacture of vinyl chloride and its polymers. J Occup Med. 1974;16:509–518. 4. Tabershaw IR. Special communication: editor’s note. J Occup Med. 1974;16:151. 5. Jones JH. Worker exposure to vinyl chloride and poly (vinyl chloride). Environ Health Perspect. 1981;41:129–136. 6. Barnes AW. Vinyl chloride and the production of PVC. Proc R Soc Med. 1976;69:277–280. 7. Ott MG, Langner RR, Holder BB. Vinyl chloride exposure in a controlled industrial environment. Arch Environ Health. 1975;31:333–339. 8. Doll R. Effects of exposure to vinyl chloride. Scand J Work Environ Health. 1988;14:61–78. 9. Falk H, Herbert J, Crowley S, et al. Epidemiology of hepatic angiosarcoma in the United States: 1964–1974. Environ Health Persp. 1981;41:107–113.
Angiosarcoma Among Vinyl Chloride Workers
10. Forman D, Bennett B, Stafford J, Doll R. Exposure to vinyl chloride and angiosarcoma of the liver: a report of the register of cases. Br J Ind Med. 1985;42:750–753. 11. Radek E. The service for the organization of postexposure medical examinations: ODIN. Int Arch Occup Environ Health. 1998;71:151–153. 12. Cooper WC. Epidemiologic study of vinyl chloride workers: mortality through December 31, 1972. Environ Health Perspect. 1981;41:101–106. 13. Wong O, Whorton MD, Foliart DE, Ragland D. An industry-wide epidemiologic study of vinyl chloride workers, 1942–1982. Am J Ind Med. 1991;20:317–334. 14. Wong O, Whorton MD, Ragland D, Klassen C, Samuels D, Claxton K. An Update of an Epidemiologic Study of Vinyl Chloride Workers, 1942–1982. 1986. 15. Mundt KA, Dell LD, Austin RP, Luippold RS, Noess R, Bigelow C. Historical cohort study of 10 109 men in the North American vinyl chloride industry, 1942–72: update of cancer mortality to 31 December 1995. Occup Environ Med. 2000;57:774–781. 16. Ward E, Boffetta P, Andersen A, et al. Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry. Epidemiology. 2001;12:710–718. 17. Bolt H. Extremely long latency of hepatic angiosarcoma in a vinyl chloride autoclave worker. EXCLI J. 2009;8:30–34. 18. IARC. 1,3-Butadiene, ethylene oxide and vinyl halides (vinyl fluoride, vinyl chloride and vinyl bromide). Lyon, France: International Agency for Research on Cancer; 2008. 19. Cook RR, Ott MG. Health Surveillance Vinyl Chloride Workers—Midland Division. 1974. 20. Dahar WS, Bond GG, McLaren EA, Sabel FL, Lipps TE, Cook RR. Update to vinyl chloride mortality study. J Occup Med. 1988;30:648–649. 21. Buffler PA, Wood S, Eifler C, Suarez L, Kilian DJ. Mortality experience of workers in a vinyl chloride monomer production plant. J Occup Med. 1979;21:195–203. 22. Bond GG, McLaren EA, Sabel FL, Bodner KM, Lipps TE, Cook RR. Liver and biliary tract cancer among chemical workers. Am J Ind Med. 1990;18: 19–24. 23. Burns C, Harrison K, Jammer B, Zuccarini D, Lafrance B. A cancer incidence and mortality study of Dow Chemical Canada Inc. manufacturing sites. Occup Med. 2005;55:618–624. 24. Burns CJ, Bodner KM, Jammer B, Collins JJ, Swaen G. Mortality surveillance of a US wide cohort of chemical workers. J Occup Environ Med. 2010;52:982– 987. 25. Burns CJ, Cartmill JB, Carson ML. Cause-specific mortality among employees of a Texas-based chemical manufacturing facility, 1940 through 1996. Texas Med. 2003;99:67–73. 26. Burns CJ, Cartmill JB, Chau M. Cause-specific mortality among Michigan employees of a chemical company: 1940 to 1994. J Occup Environ Med. 2002;44:168–175. 27. Olsen GW, Lacy SE, Cartmill JB, et al. Half-century of cause-specific mortality experience of chemical manufacturing employees. Am J Ind Med. 1994;26:203–219. 28. Bond GG, McLaren EA, Cartmill JB, Wymer KT, Lipps TE, Cook RR. Mortality among female employees of a chemical company. Am J Ind Med. 1987;12:563–578. 29. Bond GG, McLaren EA, Cartmill JB, et al. Cause-specific mortality among male chemical workers. Am J Ind Med. 1987;12:353–383. 30. Bond GG, Shellenberger RJ, Fishbeck WA, et al. Mortality among a large cohort of chemical manufacturing employees. J Natl Cancer Inst. 1985;75:859– 865. 31. Vianna NJ, Brady J, Harper P. Angiosarcoma of the liver: a signal lesion of vinyl chloride exposure. Environ Health Perspect. 1981;41:207–210. 32. Molina E, Hernandez A. Clinical manifestations of primary hepatic angiosarcoma. Dig Dis Sci. 2003;48:677–682. 33. Mundt KA, Dell LD, Austin RP, Luippold RS. Epidemiological Study of Men Employed in the Vinyl Chloride Industry Between 1942 and 1972: I Reanalysis of Mortality Through December 31, 1982; and II Update of Mortality Through December 31, 1995. Amherst, MA: Applied Epidemiology Inc; 1999.
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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Surveillance for Angiosarcoma of the Liver Among Vinyl Chloride Workers James J. Collins, PhD, Brenda Jammer, BS, Frank M. Sladeczek, MD, Catherine M. Bodnar, MD, and Sergio S. Salomon, MD
Objective: We report the results of our angiosarcoma of the liver (ASL) registry to assess the occurrence, the impact of exposures to vinyl chloride, and to quantify latency. Methods: We examined more than 73,000 death certificates of North American workers employed between 1940 and 2008. Results: We found 13 deaths of ASL among workers with vinyl chloride exposure. All 13 occurred at single plant among workers with high vinyl chloride exposure. The mean latency after first exposure was 36.5 years ranging from 24 to 56 years. No ASL deaths occurred among workers with vinyl chloride exposures after 1974, when exposures were reduced. Conclusions: We may have seen the last case of ASL among workers exposed to vinyl chloride. Nevertheless, given the long latency of this cancer, continued surveillance seems prudent.
I
n the early 1970s, an experimental study indicated that exposure to vinyl chloride may cause cancer.1 Soon after, the Goodrich Chemical Company reported that three of its workers employed in the manufacturing of vinyl chloride resins had died of rare tumor, angiosarcoma of the liver (ASL).2 Workers at this plant were part of a North American industry-wide study of workers exposed to vinyl chloride, which reported initial results in 1974, including an increased risk of ASL.3 An experimental study in rats also reported an increase in this rare cancer after exposure.4 Given the findings from these studies, steps were taken to reduce vinyl chloride exposure across the industry.5–7 Several epidemiology studies were begun,8 and surveillance for this rare cancer was undertaken by both government and industry.9–11 Today, the two largest epidemiology studies on workers exposed to vinyl chloride are the North American and the European industry-wide studies. The North American study has been updated three times.12–15 The most recent update of this study found 48 angiosarcomas of the liver among 80 liver cancer deaths.15 The findings of the North American study are very similar to a European industry-wide study of vinyl chloride monomer workers, which found 37 angiosarcomas among 53 deaths from liver cancer.16 These studies and registries indicate that the risk of this rare cancer associated with vinyl chloride exposure extended across regions and might have a long latent period after first exposure extending beyond 35 years.10,17 The International Agency for Research on Cancer currently classifies vinyl chloride as carcinogenetic to humans based on sufficient evidence of increased risk of angiosarcomas of the liver and hepatocellular carcinomas.18 The Dow Chemical Company plants of Midland, Plaquemine, Sarnia, Freeport, South Charleston, and Texas City are included in the North American industry-wide study. The South Charleston and Texas City plants were originally part of Union Carbide until a merger with Dow in 2001. The company offers periodic medical examinations to its workers. A company disease registry for ASL was established in 1974.19 Individual epidemiology studies of cancer risk from vinyl chloride exposure have also been undertaken at some of From The Dow Chemical Company, Midland, Mich. Source of funding: The Dow Chemical Company. Conflicts of interest: None. Address correspondence to: James J. Collins, PhD, The Dow Chemical Company, 1803 Building, Midland, MI 48674 ([email protected]). C 2014 by American College of Occupational and Environmental Copyright Medicine DOI: 10.1097/JOM.0000000000000247
these locations.7,20–22 In addition, plant-wide mortality studies have also been done at sites where vinyl chloride monomer exposure was possible.23–30 We report the results of our most recent update of this ASL registry to assess the occurrence of new cases of this liver cancer, to assess exposures and latency periods of the occurrence of all cases, and to determine whether continued surveillance is needed.
METHODS Angiosarcoma of the liver is a rare cancer making up less than 1% of the primary hepatic tumors in the general population.31,32 It is an aggressive malignancy that is rapidly fatal and difficult to diagnose without liver biopsy.32 The Dow Epidemiology Department has established a database to collect employee demographic, vitals status, death certificates, and work history, and address data on all full-time US employees who worked more than 3 days since January 1, 1940. Currently, we have 189,572 current or former North American workers in this system. Of these, 74,759 are deceased and we have death certificates on 73,925 of the decedents (98.8%). The sources of data on vital status and deaths include internal pension information and external sources, including the National Death Index, states’ vital statistics offices, the Social Security Administration, credit bureaus, and state motor vehicle departments. In our registry, cases of angiosarcoma of liver were identified from death certificates with histology confirmation prior to 1990. These cases are also recorded in the angiosarcoma liver registry for vinyl chloride workers by the Association of Plastic Manufacturers.10 After 1990, we relied primarily on death certificates to identify new deaths from this cancer because obtaining pathology reports has become more difficult. For the United States, we searched all death certificates from January 1, 1940, to December 31, 2011, for “angiosarcoma of the liver,” “hemangiosarcoma,” or “angiosarcoma” as an underlying, contributing, or condition present at death. We also examined death certificate codes under versions of the International Classification of Diseases (ICD) where ASL cases may be coded to assure that we did not miss any cases in our initial review (ICD-10: C22-C24, C49, C78.7). For our two Canadian plants, we included all workers employed for 12 months between 1950 and 1996 and searched the Canadian Mortality Data Base from 1950 to 1996.23 As mentioned previously, there was an effort to reduce vinyl chloride monomer exposures across the North America industry in 1974 and there is evidence that this reduction was successful.5–7,21 These reductions were from several hundred parts per million (ppm) to 5 ppm or less. Thus, vinyl chloride exposures pre- and post-1974 were very different and may be important for assessing ASL risk. We identified workers employed at any of the six aforementioned plants that were included in the North American industry-wide study.15 That study included workers who worked for at least 1 year in a job where there was exposure to vinyl chloride between January 1, 1942, and December 31, 1972. In our assessment, all workers with potential exposure to vinyl chloride were included, regardless of duration of possible exposure. This would include workers exposed less than 1 year, workers with intermittent exposures, and exposures that occurred before 1942 and after 1972. We also included workers who worked in maintenance jobs with plant-wide responsibilities as
JOEM r Volume 56, Number 11, November 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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TABLE 1. Potential Deaths From Angiosarcoma of the Liver Identified From the Dow Angiosarcoma of the Liver Registry
Site Plants w/o VCM exposure Plants with VCM exposure 1. Midland 2. South Charleston 3. All other plants Total
Potential Deaths From Angiosarcoma
Angiosarcoma of the Liver Listed on Death Certificate or Histology Report
Job Listed on Work History With Potential Vinyl Chloride Exposure
Potential Exposure and Angiosarcoma of the Liver Diagnosis
Included in North American Industry Wide Study
Identified as Angiosarcoma of the Liver in North American Industry-wide Study
1 19 4 15 0 20
1 14 1 13 0 15*
0 15 0 15 0 15†
0 13 0 13 0 13
NA 13 NA 13 NA 13
NA 11 NA 11 NA 11‡
*The five deaths that were not angiosarcoma of the liver were deaths from angiosarcoma of the heart (1), angiosarcoma of the spine (1), angiosarcoma of the knee (1), angiosarcoma of the scalp (1), and angiosarcoma of the lung (1). †Five workers had no indication of exposure to vinyl chloride on their Dow work history. Nevertheless, two workers had general maintenance jobs with potential exposure. We classified these two workers as exposed. ‡The two deaths were not included in the most recent North American Industry-wide study. One case of angiosarcoma of the liver occurred after the end date of the study and the other had liver failure as the cause of death but additional information indicated it was angiosarcoma of the liver. NA, not applicable; VCM, vinyl chloride monomer.
6
having potential exposure. Review and oversight were provided by a human subjects review board in Midland, Michigan.
5
RESULTS
DISCUSSION Establishing an ASL disease registry for workforces with potential exposure to vinyl chloride is useful because this cancer is rare in humans and has been associated with only a few workplace exposures including vinyl chloride, and the latency period seems to 1208
4 Number
We identified 20 deaths with “angiosarcoma of liver,” “hemangiosarcoma,” or “angiosarcoma” from any our death certificates or from additional information from histology reports as shown in Table 1. Only 15 of these deaths were ASL. The other 5 deaths were angiosarcoma at sites other than the liver. Fifteen of the 20 deaths also had potential exposure to vinyl chloride according to their work histories and all 15 were located at the South Charleston plant. Thirteen deaths, all at the South Charleston plant, had both a diagnosis of ASL and potential exposure to vinyl chloride. All 13 workers with the diagnosis were included in the North American industrywide study. The exposure estimates developed for that plant for the study indicated that all decedents had high exposures to vinyl chloride. Eleven of the 13 were identified as angiosarcoma of liver in the North American industry-wide vinyl chloride worker study.15,33 One of the two deaths not included occurred after the North American study end date and the other that was listed as a “liver failure” on the death certificate. Additional histology information indicated that this case was an ASL. We did observe two deaths from ASL that occurred among workers without exposure to vinyl chloride according to their work history. One worker was employed at a plant with no vinyl chloride exposure and the other worked at a plant with vinyl chloride but in a job and department with no potential for exposure. Figure 1 presents the deaths for ASL by decade of death. Ten of the 13 deaths occurred in the 1970s and 1980s. The decades of the 1960s, 1990s, and the period 2000–2011 each reported a single death from this disease with the first death reported in 1968 and the latest death occurring in 2002. We also examined year of first exposure for the ASL cases. Twelve of the 13 workers were first exposed to vinyl chloride between the years 1940 and 1949. The remaining worker was first exposed in 1965. The mean number of years between first exposure and death was 36.5 years ranging from 24 to 56 years.
3 2 1 0 1960's
1970's
1980's
1990's
2000's
FIGURE 1. Deaths from angiosarcoma of the liver among workers with potential vinyl chloride exposure by decade of death.
be very long. We have been successful in establishing our registry of angiosarcoma of liver deaths because we routinely collect demographics, company work history, vital status of all former workers, and death certificates for all deceased workers for our US workforce. For our Canadian sites, we do periodic plant-wide assessments but have limited access to the death certificates to comply with Canadian confidentiality laws. In this registry, we identified 15 cases of ASL. Thirteen of these cases were among workers at a single plant all with high vinyl chloride exposure occurring before 1974. We found no cases of ASL among workers with vinyl chloride exposures after 1974. The risk of ASL has been related to very high exposures to vinyl chloride.16 The fact that all of the deaths related to ASL occurred at a single plant could indicate that exposures were higher at this location than at the other locations. The limited information we have on historical exposures at these plants in the registry supports this conclusion.7,15,21 We also identified two deaths of ASL among workers who did not have Dow workplace exposure to vinyl chloride. Angiosarcoma of the liver has other environmental causes other than vinyl chloride monomer and some cases are idiopathic. These two deaths out of the more 70,000 deaths we reviewed are consistent with background rates of ASL reported for the United States.31
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JOEM r Volume 56, Number 11, November 2014
There are some limitations to this study. First, the diagnosis for ASL has not been verified by histology reports in recent years but relies solely on causes recorded on the death certificate. The death certificate is an unreliable source of information about the histology of liver cancer.8,15 It is possible that some angiosarcomas of the liver were not reported in our registry but were recorded simply as liver cancer or liver failure on the death certificate. We observed an example of this type of underreporting of an ASL case in the North American industry-wide study where the death certificate listed “liver failure” as the underlying cause of death. Nevertheless, given the amount of public attention the association between vinyl chloride exposure and angiosarcoma of liver has received, we think it unlikely that the number of cases missed would be significant in either this study or the North American industry-wide study. We also observed three angiosarcomas at sites other than the liver among the South Charleston plant workers. Like ASL, these are relatively rare tumors. Mundt and colleagues15 observed an excess of soft tissues sarcomas in general among the North American vinyl chloride workers including angiosarcomas at other sites. Because of coding conventions for causes of death, many of these soft tissue tumors are grouped with other cancers at the same anatomical site, making it difficult to analyze them as a group. Another limitation of our registry is that the exposure characterization to vinyl chloride, especially exposures in the early years, is limited by lack of monitoring information, making it difficult to compare plants by exposure levels. All of the cases in our registry were first exposed to vinyl chloride before 1974, with all but one of the cases exposed before 1950. The most recent death occurred in 2002, and no additional cases have been observed in the past 7 years of observation. The mean latency period for ASL after first vinyl chloride exposure was 36.5 years in our registry. We have seen no deaths from ASL among workers first exposed after 1974 at several plants when exposures to vinyl chloride were much lower. We may have seen the last case of ASL among our workers exposed to vinyl chloride. Although our findings are based on a single company’s experience, we find no evidence of increased risk of ASL among workers with low vinyl chloride exposure. Nevertheless, given the long latency of this cancer, continued surveillance seems prudent.
REFERENCES 1. Viola PL, Bigotti A, Caputo A. Oncogenic response of rat skin, lungs and bones to vinyl chloride. Cancer Res. 1971;31:516–519. 2. Creech JL, Johnson MN. Angiosarcoma of liver in the manufacture of polyvinyl chloride. J Occup Med. 1974;16:150–151. 3. Tabershaw IR, Gaffey WR. Mortality study of workers in the manufacture of vinyl chloride and its polymers. J Occup Med. 1974;16:509–518. 4. Tabershaw IR. Special communication: editor’s note. J Occup Med. 1974;16:151. 5. Jones JH. Worker exposure to vinyl chloride and poly (vinyl chloride). Environ Health Perspect. 1981;41:129–136. 6. Barnes AW. Vinyl chloride and the production of PVC. Proc R Soc Med. 1976;69:277–280. 7. Ott MG, Langner RR, Holder BB. Vinyl chloride exposure in a controlled industrial environment. Arch Environ Health. 1975;31:333–339. 8. Doll R. Effects of exposure to vinyl chloride. Scand J Work Environ Health. 1988;14:61–78. 9. Falk H, Herbert J, Crowley S, et al. Epidemiology of hepatic angiosarcoma in the United States: 1964–1974. Environ Health Persp. 1981;41:107–113.
Angiosarcoma Among Vinyl Chloride Workers
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