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Description of key information

Vinyl chloride is a multi-site carcinogen in animals inducing angiosarcomas at many sites (though predominantly liver), hepatocellular tumours, tumours of the mammary, and lung tumours.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
0.13 mg/kg bw/day

Carcinogenicity: via inhalation route

Endpoint conclusion
Dose descriptor:
130 mg/m³

Justification for classification or non-classification

Vinyl chloride is a known carcinogen, which is classified as carcinogenic category 1 (Carc. Cat. 1; R45) according to EU Directive 67/548/EEC, and as Cat. 1A (H350) according to criteria of the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.


Additional information

Available chronic exposure animal studies with vinyl chloride indicate that long term exposure causes cancer. Vinyl chloride is a multi-site carcinogen in animals inducing angiosarcomas at many sites (though predominantly liver), hepatocellular tumours, tumours of the mammary, and lung tumours.

As vinyl chloride is a gas, inhalation is considered to be the most relevant exposure route.

A LOAEC of 50 ppm (130 mg/m3) was established by Lee et al. in a 12 months inhalation study with rats, based on occasional occurrence of hemangiosarcoma in several tissues, including omentum, mesentery or subcutaneous tissue. Hepatic and/or pulmonary hemangiosarcoma occurred in rats at higher exposure levels; the incidence increased with increases in VC levels and length of exposure. The same LOAEC was determined in mice.

Occupational vinyl chloride exposure was first associated with development of liver cancer in 1974, when rare liver angiosarcomas were detected in three workers who worked in a vinyl chloride polymerization plant. Worker cohorts employed in the vinyl chloride industry in theandhave been studied extensively over the last 25 years and confirm earlier findings of an increased incidence of angiosarcoma in humans that are occupationally exposed. The discussion on the other tumours as being vinyl chloride-related is still ongoing (Swaen and Dujits, 2005; Grosse et al., 2007).

 Also two combined chronic toxicity/carcinogenicity oral studies were available for assessment, in which rats were exposed via diet to polyvinyl chloride (PVC) powder enriched with vinyl chloride monomer. A NOAEL of 0.13 mg/kg bw/day was established by Til and co-workers (1991), based on increased mortality in females, liver cell changes and occurrence of hepatocellular carcinoma and angiosarcoma. Feron et al. (1981) established a LOAEL of 1.7 mg/kg bw/day, based on liver cell changes and occurrence of hepatocellular carcinoma. In addition, hepatic, pulmonary and abdominal angiosarcoma and Zymbal gland tumours were found in rats at higher exposure levels. These findings are supported by the studies of Maltoni et al.; however, these studies are considered to be less reliable in comparison to the key studies identified above. In addition, as numerous human data on vinyl chloride are available, these data are considered as critical for the conclusion on carcinogenicity.

Human data on the carcinogenicity of vinyl chloride were assessed by International Agency for Research on Cancer (IARC) (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 97, 2008, and references therein)). Principally, the evidence on the carcinogenicity of vinyl chloride derives from two large, multicentric cohort studies, one of which was carried out in North America and the other in, focusing on plants manufacturing vinyl chloride monomer, polyvinyl chloride or polyvinyl chloride products. Both studies found a substantial increase in the relative risk for liver angiosarcoma in the exposed workers, a tumour that is extremely rare in the general population. In both studies, the risk for liver angiosarcoma increased strongly with duration of exposure to vinyl chloride; in the European study, also a clear trend of higher risk was observed with increasing cumulative exposure. Overall, IARC concluded that these findings provide clear evidence that exposure to vinyl chloride causes angiosarcoma of the liver. 

In addition, the risk for hepatocellular carcinoma was found to increase significantly with cumulative exposure to vinyl chloride in an internal analysis of the European multicentric cohort, based on nine confirmed cases. 12 confirmed cases of hepatocellular carcinomas were also found in the analysis of a single Italian plant with extended follow-up that was included in the European multicentric study. In this subcohort, the incidence of hepatocellular carcinoma again increased significantly with cumulative exposure to vinyl chloride. Based on these results together with the observation that vinyl chloride increases the risk for liver cirrhosis, which is a known risk factor for hepatocellular carcinoma, IARC concluded that these findings provide convincing evidence that vinyl chloride causes hepatocellular carcinoma as well as angiosarcoma of the liver.


No evidence of an increased risk for lung cancer was observed in either cohort among vinyl chloride workers overall. Among the other cancer sites, suggestive evidence was found for malignant neoplasms of connective and soft tissue. This evidence was derived from the multicentric study in; however, these findings were not supported by the European multicentric study, in which too few cases of connective tissue neoplasms were observed for an evaluation of exposure–response. No strong epidemiological evidence for associations of exposure to vinyl chloride with cancers of the brain or lymphatic and haematopoeitic tissue or melanoma was found. No conclusion could be reached for breast cancer since the studies included too few women.

In conclusion, there is a clear evidence that exposure to vinyl chloride is associated with the increased risk of cancer in humans and experimental animals. In humans, vinyl chloride causes angiosarcomas of the liver and hepatocellular carcinomas. Based on these data, IARC concluded that vinyl chloride is carcinogenic to humans (Group 1).

Comment on the relationship between exposure to VCM and the incidence of Hepatocellular Carcinoma in humans.
The WHO International Agency for Research on Cancer (IARC) have concluded that, in addition to leading to angiosarcoma of the liver, there is “sufficient evidence” that exposure to VCM increases the risk of hepatocellular carcinoma (HCC).
The epidemiological evidence that VCM is a causative factor in the development of HCC is weak: the risk ratio for development of HCC in VCM-exposed individuals is only 1.3. This elevation is extremely small (the lower 95% confidence limit is 1.03). In addition, since the epidemiological studies were based on the identification of  non specified “liver cancer” as the cause of death on death certificates, it is very likely that some of the tumours thus classified were not actually HCCs but were angiosarcomas or  other liver cancers than HCC or metastases from primary tumours arising elsewhere in the body.
The role of other common risk factors for HCC (viral infection and alcohol abuse) was not taken into account adequately in the studies reviewed by IARC. These factors are thought to account for more than 90% of all cases of HCC. It is possible  but not proven  that exposure to VCM may have an indirect effect by promoting the development of HCCs caused by these factors.
Animal studies have not shown a clear relationship between exposure to VCM and the induction of HCC, even in strains of mice that are particularly sensitive to the development of these tumours.
Overall, therefore, the evidence supporting the hypothesis that exposure to VCM leads to an increased incidence of HCC is extremely weak and the data are insufficient for conclusions to be drawn concerning their distribution.

Carcinogenicity: via inhalation route (target organ): digestive: liver