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http://ehpnet1.niehs.nih.gov/docs/2000/108p579-588kielhorn/abstract.html
Environmental Health Perspectives Volume 108, Number 7, July 2000
Vinyl Chloride: Still a Cause for Concern
Janet Kielhorn,1 Christine Melber,1 Ulrich Wahnschaffe,1 Antero Aitio,2 and
Inge Mangelsdorf1
1Fraunhofer Institute for Toxicology and Aerosol Research with Drug Research
and Clinical Inhalation, Hanover, Germany; 2International Programme on
Chemical Safety, World Health Organization, Geneva, Switzerland
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Abstract
Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and
its production capacity has almost doubled over the last 20 years, currently
27 million tons/year worldwide. According to recent reports it is still a
cause for concern. VC has been found as a degradation product of
chloroethylene solvents (perchloroethylene and trichloroethylene) and in
landfill gas and groundwater at concentrations up to 200 mg/m3 and 10 mg/L,
respectively. Worldwide occupational exposure to VC still seems to be high
in some countries (e.g., averages of approximately 1,300 mg/m3 until 1987 in
one factory), and exposure may also be high in others where VC is not
regulated. By combining the most relevant epidemiologic studies from several
countries, we observed a 5-fold excess of liver cancer, primarily because of
a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of
ASL cases reported up to the end of 1998 was 197 worldwide. The average
latency for ASL is 22 years. Some studies show a small excess risk for
hepatocellular carcinoma, and others suggest a possible risk of brain tumors
among highly exposed workers. Lung cancer, lymphomas, or leukemia do not
seem to be related to VC exposure according to recent results. The mutation
spectra observed in rat and human liver tumors (ASL and/or hepatocellular
carcinoma) that are associated with exposure to VC are clearly distinct from
those observed in sporadic liver tumors or hepatic tumors that are
associated with other exposures. In rats, the substitution mutations found
at A:T base pairs in the ras and p53 genes are consistent with the
promutagenic properties of the DNA adduct 1,N6-ethenoadenine formed from VC
metabolites. Risk assessments derived from animal studies seem to
overestimate the actual risk of cancer when comparing estimated and reported
cases of ASL. Key words: angiosarcoma of the liver (ASL), landfill leachate,
liver cancer, occupational exposure, risk assessment, vinyl chloride.
Environ Health Perspect 108:579-588 (2000). [Online 2 June 2000]
http://ehpnet1.niehs.nih.gov/docs/2000/108p579-588kielhorn/abstract.html
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Address correspondence to J. Kielhorn, Fraunhofer Institute for Toxicology
and Aerosol Research, Nikolai-Fuchs Strasse 1, D-30625 Hanover, Germany.
Telephone: 49 (511) 5350 329. Fax: 49 (511) 5350 335. E-mail:
kielhorn@ita.fhg.de
This paper is based on work performed by the authors in preparation of the
International Programme on Chemical Safety (IPCS) draft document on vinyl
chloride. This paper is the sole responsibility of the authors.
IPCS Task Group members were A. Barbin, V. Feron, P. Heikkila, J. Kielhorn,
M. Kogevinas, H. Malcolm, W. Pepelko, A. Pinter, L. Simonato, H. Vainio, E.
Ward, and J. Zielinski.
We acknowledge the financial support of the German Federal Ministry for the
Environment, Nature Conservation and Nuclear Safety.
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