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Vinyl chloride: an assessment of the risk of occupational exposure.

作者信息

Purchase I F, Stafford J, Paddle G M

出版信息

Food Chem Toxicol. 1987 Feb;25(2):187-202. doi: 10.1016/0278-6915(87)90153-0.

DOI:10.1016/0278-6915(87)90153-0
PMID:3549485
Abstract

There is little doubt that exposure to high levels of VCM as a consequence of occupation can result in an increased incidence of ASL. A review of 20 epidemiological studies involving about 45,000 workers occupationally exposed to VCM showed that neoplasms of the liver showed an increase in incidence in the majority of studies. For brain cancer the association between exposure to VCM and an increased incidence was less clear because of the lower relative risk. Neoplasms of the respiratory tract, digestive system, lymphatic and haemopoietic system, buccal cavity, and pharynx, cardiovascular system and colon/stomach were reported to show an increased incidence in one or more studies, but to show no increase, or in some cases a decrease, in incidence in other studies. In view of the increased incidence of breast neoplasms in rodents exposed to VCM, the studies of Chaizze et al. (1980), who did not confirm these findings in humans, are of importance. The register of ASL cases now contains records of 99 persons with confirmed ASL and occupational exposure to VCM. The average latent period between first exposure to VCM and death from ASL is 21.9 years. The majority of cases occurred in autoclave workers, who are recognized as having been exposed to extremely high levels. Although precise estimates of exposure are not available for the periods of most interest, the pattern of cases roughly suggests that extremely high exposures were necessary for the induction of ASL. For example, ASL cases tended to occur in larger numbers in some plants than in others, a finding that can be explained most easily by differences in exposure patterns. There is an extensive series of animal studies on the carcinogenicity of VCM. Some of these precede the epidemiological studies confirming the association between VCM exposure and ASL in man. ASL and neoplasms of a number of other organs have been induced in laboratory rodents by VCM. Estimation of the exposure levels likely to cause a lifetime risk of ASL of 10(-6) on the basis of these data give extremely low levels (down to 3.9 X 10(-7) ppb) which appear to be unrealistic estimates for man. Part of the reason for this is that laboratory studies have shown that VCM is metabolized in the liver (and elsewhere in the body) to the reactive metabolites chloroethylene oxide and chloroacetaldehyde. The rate of conversion is limited at high levels of exposure giving inaccurate estimates of the slope of the dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

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Development and application of an LC-MS/MS method for the detection of the vinyl chloride-induced DNA adduct N(2),3-ethenoguanine in tissues of adult and weanling rats following exposure to [(13)C(2)]-VC.
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Vinyl chloride: still a cause for concern.氯乙烯:仍然令人担忧。
Environ Health Perspect. 2000 Jul;108(7):579-88. doi: 10.1289/ehp.00108579.
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All four known cyclic adducts formed in DNA by the vinyl chloride metabolite chloroacetaldehyde are released by a human DNA glycosylase.氯乙烯代谢产物氯乙醛在DNA中形成的所有四种已知环状加合物都由一种人类DNA糖基化酶释放出来。
Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1024-8. doi: 10.1073/pnas.91.3.1024.