A Summation of IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 97, 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide).
Background: The International Agency for Research on Cancer (IARC) was created in 1965 by the World Health Organization (WHO). Since their inception, the IARC constantly “…received requests for advice on the carcinogenic risk of chemicals, including requests for lists of known and suspected carcinogens” (IARC, 2008, p. 9).
Thus, in 1970, the IARC Governing Council determined that the IARC will provide government authorities with expert scientific opinion on carcinogenesis. The Governing Council’s determination led to the development of the IARC Monographs on the Evaluations of Carcinogenic Risks to Humans.
Thus, in 1970, the IARC Governing Council determined that the IARC will provide government authorities with expert scientific opinion on carcinogenesis. The Governing Council’s determination led to the development of the IARC Monographs on the Evaluations of Carcinogenic Risks to Humans.
The multiple volumes of monographs are used by government authorities worldwide for making risk assessments, deciding preventive measures, and providing cancer control programs (IARC, 2008). A working group of experts publish the monographs after a critical review process and evaluation of evidence on the carcinogenicity of human exposure to an agent. An evaluation of an agent is based on scientific findings of evidence from extensive studies in humans and experimental animals. The agent is categorized and set to a criterion of the following groups:
Group 1: The agent is carcinogenic to humans. Meaning there is sufficient evidence of carcinogenicity in humans or less the sufficient in humans but sufficient in experimental animals and strong evidence in exposed humans.
Group 2A: The agent is probably carcinogenic to humans. Meaning there is limited evidence of carcinogenicity in humans and sufficient in experimental animals.
Group 2B: The agent is possibly carcinogenic to humans. Meaning there is limited evidence of carcinogenicity in humans and less than sufficient in experimental animals.
Group 3: The agent is not classifiable as to its carcinogenicity to humans. Meaning there is inadequate evidence of carcinogenicity in humans and inadequate or limited in experimental animals.
Group 4: The agent is probably not carcinogenic to humans. Meaning there is evidence suggesting lack of carcinogenicity in humans and in experimental animals.
Group 2A: The agent is probably carcinogenic to humans. Meaning there is limited evidence of carcinogenicity in humans and sufficient in experimental animals.
Group 2B: The agent is possibly carcinogenic to humans. Meaning there is limited evidence of carcinogenicity in humans and less than sufficient in experimental animals.
Group 3: The agent is not classifiable as to its carcinogenicity to humans. Meaning there is inadequate evidence of carcinogenicity in humans and inadequate or limited in experimental animals.
Group 4: The agent is probably not carcinogenic to humans. Meaning there is evidence suggesting lack of carcinogenicity in humans and in experimental animals.
Introduction: The IARC Monograph Vol. 97 classified Vinyl Chloride as a Group1 agent, “Carcinogenic to Humans.” Vinyl chloride is used for making Polyvinyl Chloride (PVC) and PVC resin is used primarily for the production of plastics for consumer and industrial products. Vinyl chloride is produced worldwide and has been in production in the U.S. for over 70 years. The primary route of occupational exposure is inhalation which normally occurs at vinyl chloride and PVC production plants. The IARC Monograph, Table 4 displays workplace exposure levels in the U.S. as followed: CGIH TWA = 1 ppm; OSHA PEL = 1 ppm and STEL = 5 ppm (IARC, 2008, p. 322).
Overview: Studies of cancer in humans for vinyl chloride were highlighted in a 1974 case report from the Journal of Occupational Medicine. The report identified an extremely rare tumor (angiosarcoma) of the liver which had developed in three men who had worked in a PVC resin manufacturing plant. Since then, several cohort studies have been conducted which include two epidemiological multicentric investigations of workers employed in the vinyl chloride industry. One epidemiological study was conducted in Europe and one in North America. The following link is the outline of data on the studies of cancer in humans: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8B.pdf
The initial North American multicentric study included 10,173 workers from 37 plants. Eligible study participants were male employees who were exposed to vinyl chloride for at least one year and who worked at the plants from 1942 – 1972. A second follow-up study was conducted with statistics through 1989 (with original 10,173 participant data) and a third major update (after minor corrections to study records, included 10,109 of the test subjects). The IARC Monograph, Table 5 displays the data of the cohort studies of liver and biliary tract cancer in vinyl chloride production workers (IARC, 2008, p. 333). Additionally, Table 7, displays the data of the cohort studies of brain and central nervous system (CNS) cancer (p. 350); Table 8, data of cohort studies of lung cancer (p. 356); Table 10, data of lympho-haematopoietic neoplasms (p. 366); and Table 11, data of cohort studies of malignant melanoma (p. 370).
A case-study of focused on a vinyl chloride processing plant in Louisville, KY and observed 2,200 workers who had been exposed to vinyl chloride for at least one year from 1942 – 1972. A follow-up study was conducted to include data through 1995. The IARC Monograph, Table 5 included statistics for this case-study as Table 6, displays the data of the case-control study of liver cancer (p. 346); and Table 9, data of case-control studies of lung cancer (p. 362).
The European multicentric study was conducted in four countries (Italy, Norway, Sweden and the U.K.). The initial multicentric study included 12,700 workers from 19 plants. Eligible study participants were male employees who were exposed to vinyl chloride for at least a year and who worked at the plants from 1950 – 1985. A follow-up study was conducted with statistics from 1955 – 1997.
Extensive studies in experimental animals have also been conducted. The following link is the outline of the data on the studies of cancer in experimental animals: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8C.pdf
Summation: Data conclusions of all the studies were based on a standardized mortality ratio (SMR) compared to state reference rates. The results of the North American multicentric cohort study, revealed alarming SMR results. The SMR for liver and biliary tract cancer was relatively high at 3.59; well above the nominal rate (1.0) since death from liver cancer was not expected to be above 23 and 80 deaths occurred among the 10,109 subjects. On the other hand, the SMR for lung cancer was 0.82, since death from lung cancer was anticipated even though 303 deaths were observed. The SMR for brain and CNS cancer was 1.42 (36 deaths); SMR for lympho-haematopoietic neoplasms was 0.86 (71 deaths); and SMR for malignant melanoma was 0.64 (12 deaths).
The results of the Louisville, KY case-study revealed the SMR was 4.00 for liver and biliary tract cancer (24 deaths opposed to 6 expected). The IARC Monograph stated,
“The occurrence of angiosarcoma was strongly associated with exposure to vinyl chloride but not with exposure to other chemicals; the risk for brain cancer was highest among workers who had been hired before 1950 but was not associated with exposure to vinyl chloride” (p.325).
The results of the European study revealed the SMR was 2.40 for liver cancer (53 deaths); SMR was 0.93 for brain cancer (24 deaths); SMR was 0.95 for lung cancer (272 deaths); and SMR for lymphatic and haematopoeitic cancer was 0.94 (62 deaths).
Metabolic Pathway: Vinyl chloride is primarily metabolized in the liver as an oxidation reaction. The mediated oxidation is catalyzed by the enzyme cytochrome P450. A Phase I mixed function oxidase occurs during biotransformation of vinyl chloride in the liver to form the highly reactive chloroethylene oxide which then spontaneously rearranges to chloroacetalhyde and both metobolites will bond to DNA and RNA. The following link is the outline for mechanistic and other relevant data: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8D.pdf
Conclusion: The IARC Monograph, Volume 97 highlights the sufficient epidemiological evidence from the two multicentric cohort studies that identifies vinyl chloride has a Group 1 agent, “Carcinogenic to Humans.” The IARC Monograph Chapters 5 and 6 outline the summary of data and the evaluation of vinyl chloride. The following link is for Ch. 5 & 6 respectively: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8E.pdf
http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8F.pdf
Reference:
International Agency for Research on Cancer (IARC). (2008). Vinyl Chloride. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 97, 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide). Retrieved March 23, 2009 from: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8.pdf, a link retrieved from: http://monographs.iarc.fr/
The initial North American multicentric study included 10,173 workers from 37 plants. Eligible study participants were male employees who were exposed to vinyl chloride for at least one year and who worked at the plants from 1942 – 1972. A second follow-up study was conducted with statistics through 1989 (with original 10,173 participant data) and a third major update (after minor corrections to study records, included 10,109 of the test subjects). The IARC Monograph, Table 5 displays the data of the cohort studies of liver and biliary tract cancer in vinyl chloride production workers (IARC, 2008, p. 333). Additionally, Table 7, displays the data of the cohort studies of brain and central nervous system (CNS) cancer (p. 350); Table 8, data of cohort studies of lung cancer (p. 356); Table 10, data of lympho-haematopoietic neoplasms (p. 366); and Table 11, data of cohort studies of malignant melanoma (p. 370).
A case-study of focused on a vinyl chloride processing plant in Louisville, KY and observed 2,200 workers who had been exposed to vinyl chloride for at least one year from 1942 – 1972. A follow-up study was conducted to include data through 1995. The IARC Monograph, Table 5 included statistics for this case-study as Table 6, displays the data of the case-control study of liver cancer (p. 346); and Table 9, data of case-control studies of lung cancer (p. 362).
The European multicentric study was conducted in four countries (Italy, Norway, Sweden and the U.K.). The initial multicentric study included 12,700 workers from 19 plants. Eligible study participants were male employees who were exposed to vinyl chloride for at least a year and who worked at the plants from 1950 – 1985. A follow-up study was conducted with statistics from 1955 – 1997.
Extensive studies in experimental animals have also been conducted. The following link is the outline of the data on the studies of cancer in experimental animals: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8C.pdf
Summation: Data conclusions of all the studies were based on a standardized mortality ratio (SMR) compared to state reference rates. The results of the North American multicentric cohort study, revealed alarming SMR results. The SMR for liver and biliary tract cancer was relatively high at 3.59; well above the nominal rate (1.0) since death from liver cancer was not expected to be above 23 and 80 deaths occurred among the 10,109 subjects. On the other hand, the SMR for lung cancer was 0.82, since death from lung cancer was anticipated even though 303 deaths were observed. The SMR for brain and CNS cancer was 1.42 (36 deaths); SMR for lympho-haematopoietic neoplasms was 0.86 (71 deaths); and SMR for malignant melanoma was 0.64 (12 deaths).
The results of the Louisville, KY case-study revealed the SMR was 4.00 for liver and biliary tract cancer (24 deaths opposed to 6 expected). The IARC Monograph stated,
“The occurrence of angiosarcoma was strongly associated with exposure to vinyl chloride but not with exposure to other chemicals; the risk for brain cancer was highest among workers who had been hired before 1950 but was not associated with exposure to vinyl chloride” (p.325).
The results of the European study revealed the SMR was 2.40 for liver cancer (53 deaths); SMR was 0.93 for brain cancer (24 deaths); SMR was 0.95 for lung cancer (272 deaths); and SMR for lymphatic and haematopoeitic cancer was 0.94 (62 deaths).
Metabolic Pathway: Vinyl chloride is primarily metabolized in the liver as an oxidation reaction. The mediated oxidation is catalyzed by the enzyme cytochrome P450. A Phase I mixed function oxidase occurs during biotransformation of vinyl chloride in the liver to form the highly reactive chloroethylene oxide which then spontaneously rearranges to chloroacetalhyde and both metobolites will bond to DNA and RNA. The following link is the outline for mechanistic and other relevant data: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8D.pdf
Conclusion: The IARC Monograph, Volume 97 highlights the sufficient epidemiological evidence from the two multicentric cohort studies that identifies vinyl chloride has a Group 1 agent, “Carcinogenic to Humans.” The IARC Monograph Chapters 5 and 6 outline the summary of data and the evaluation of vinyl chloride. The following link is for Ch. 5 & 6 respectively: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8E.pdf
http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8F.pdf
Reference:
International Agency for Research on Cancer (IARC). (2008). Vinyl Chloride. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 97, 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide). Retrieved March 23, 2009 from: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8.pdf, a link retrieved from: http://monographs.iarc.fr/
No comments:
Post a Comment