Fate of [14C]Vinyl Chloride following inhalation exposure in rats

Watanabe, P.G.; McGowan, G.R.; Madrid, E.O.; Gehring, P.J.

doi:10.1016/s0041-008x(76)80007-5

Cited by 80 publications

(21 citation statements)

References 9 publications

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“…Figure 4 illustrates the results from two inhalation experiments with rats exposed to vinyl chloride. The amount of radioactive metabolites was quantified following exposure to 14 carbon-labeled vinyl chloride in one experiment (42), and the incidence of liver angiosarcoma following chronic exposures was assessed in the other (43). Both the tumor response and the metabolism of vinyl chloride appear to attenuate at exposure levels exceeding 500 ppm.…”

Section: Saturation Of Effectmentioning

confidence: 99%

Attenuation of exposure-response curves in occupational cohort studies at high exposure levels

Stayner¹,

Steenland²,

Dosemeci

et al. 2003

Scand J Work Environ Health

157

119

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Section: Saturation Of Effectmentioning

confidence: 99%

Attenuation of exposure-response curves in occupational cohort studies at high exposure levels

Stayner¹,

Steenland²,

Dosemeci

et al. 2003

Scand J Work Environ Health

157

119

View full text Add to dashboard Cite

“…The pharmacokinetics and tissue distribution of 14C-labeled VCM in rats exposed by various routes to different concentrations was reported by Watanabe et al (16,17). For animals exposed to 1000 ppm 14C-VCM for 6 hr, 56% of the radioactivity was excreted in urine, 12% was expired as VCM, 12% was expired as 14CO., and 4% was found in the feces within 72 hr.…”

Section: Metabolismmentioning

confidence: 81%

“…Following a single intravenous injection of 250 uag/kg 14C-VCM, 80% of the radioactivity was detected within a few minutes in the exhaled air as unchanged VCM (18). Of the various tissues examined, the liver and skin retained the highest levels of radioactivity (16,17).…”

Section: Metabolismmentioning

confidence: 99%

Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds

Bartsch¹,

Malaveille²,

Barbin³

et al. 1976

Environmental Health Perspectives

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The various adverse biological effects of vinyl chloride appear to be dependent upon the metabolic conversion of this compound into chemically reactive metabolites. The metabolism of vinyl chloride in mammals and in man, including the formation of monochloroacetic acid and some identified sulfur conjugates is reviewed. Hepatic microsomal mixed function oxidases from rats, mice, and humans were equally effective in transforming vinyl chloride into alkylating agents in vitro. Two of the enzyme reaction products, i.e., chloroethylene oxide and 2-chloroacetaldehyde, showed potent genetic activity in microorganisms and Chinese hamster V79 cells. The role of liver microsomal enzymes in the generation of electrophilic mutagenic vinyl chloride metabolites is discussed.Chlorinated hydrocarbons, such as vinyl chloride (VCM) or vinylidene chloride, are widely used in the production of plastic resins and are present in the environment (1, 2). It is now recognized that VCM is responsible for various adverse biological effects which induce neoplastic and nonneoplastic diseases in man as well as in animals (2) and that these effects seem to be attributable not to VCM itself but to reactive metabolites formed by microsomal mixed-function oxidases. Many chemical carcinogens have been shown to exert a carcinogenic effect following their metabolic activation into elctrophilic metabolites which react readily with cellular macromolecules (3). This paper is a review of results obtained in our laboratory and by others concerning the mutagenicity of VCM and related compounds and the metabolism of some of these compounds. MutagenicityThe mutagenicity of VCM has been examined in various strains of S. typhimurium in which

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“…Sulfinpyrazone is an example of a compound that uses its ability to inhibit the pharmacokinetic process to achieve the therapeutic objective (32 Hazard Profile. Vinyl chloride is a human oncogen that has been rather thoroughly investigated in regard to its oncogenic dose response and metabolism (33). The compound produces angiosarcomas in humans exposed to high levels.…”

Section: Solubilitr Fonnation Ofbladder Calculi Resulting In Tumor Fmentioning

confidence: 99%

Pharmacokinetic factors influencing risk assessment: saturation of biochemical processes and cofactor depletion.

Sumner¹,

Stevens²

1994

Environ Health Perspect

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Models generally consider risk to be a function of the hazard (toxicity) and exposure (dose). That function is best described by the dose response of the toxic effect. For any risk assessment system to be effective, it should consider that dose-response relationship. Saturation phenomena often produce nonlinear dose curves, and any risk assessment system should be able to address such effects. Physiologically based pharmacokinetics offer an approach to deal with these nonlinear responses. Some historic risk models and common saturable processes are discussed. The impact of maximum tolerated dose (MTD) on risk evaluation and the kinetics of some saturable processes are considered. Specific examples have been selected to demonstrate the importance of saturation of processes in assessing the hazard of chemicals. -Environ Health Perspect 1 02(Suppl 11): 13-22 (1994)

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Fate of [14C]Vinyl Chloride following inhalation exposure in rats

Cited by 80 publications

References 9 publications

Attenuation of exposure-response curves in occupational cohort studies at high exposure levels

Attenuation of exposure-response curves in occupational cohort studies at high exposure levels

Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds

Pharmacokinetic factors influencing risk assessment: saturation of biochemical processes and cofactor depletion.

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