Withey J R
J Toxicol Environ Health. 1976 Jan;1(3):381-94. doi: 10.1080/15287397609529338.
Finding at least 2-3 ppm and occasionally as much as 10-20 ppm of vinyl chloride monomer in a wide range of foodstuffs has prompted concern for a possible human health hazard. The recognition of vinyl chloride as a carcinogen to humans in April 1974, following the discovery of angiosarcoma as the cause of death in at least 25 workers who had been engaged in the manufacture of polyvinyl chloride, enhanced this concern with respect to the presence of vinyl chloride monomer in foods. To assess the hazard presented by the oral ingestion of vinyl chloride monomer, rats that had been surgically prepared with an indwelling jugular cannula were dosed by intragastric intubation with aqueous solutions containing up to 2.0 mg/ml vinyl chloride. Time-concentration curves were obtained from sequential samples of blood. The uptake of vinyl chloride by this route was found to be extremely rapid; peak concentrations were achieved less than 10 min after administration of the dose. Elimination from the blood compartment appeared to be biexponential. Studies with the same animal model in a single restraint cage that allowed a "head only" exposure to concentrations of vinyl chloride up to 7,000 ppm in the gas phase have shown a similar rapid uptake followed by a plateau blood concentration during several hours of exposure. On removal from the vinyl chloride atmosphere, blood levels fell rapidly to barely detectable concentrations after 2 hr. The precise kinetic coefficients that describe the distribution and elimination rates of vinyl chloride from the blood compartment were also determined from the blood concentration data after the administration of an intravenous dose of aqueous or vegetable oil solution.
在多种食品中发现至少2 - 3 ppm，偶尔高达10 - 20 ppm的氯乙烯单体，这引发了人们对其可能危害人体健康的担忧。1974年4月，在发现血管肉瘤是至少25名从事聚氯乙烯制造的工人的死因之后，氯乙烯被认定为人类致癌物，这加剧了人们对食品中氯乙烯单体存在的担忧。为了评估口服氯乙烯单体所带来的危害，对通过手术植入颈静脉插管的大鼠进行胃内插管，给予含有高达2.0 mg/ml氯乙烯的水溶液。从连续采集的血样中获取时间 - 浓度曲线。发现通过该途径摄取氯乙烯极其迅速；给药后不到10分钟就达到了峰值浓度。血液中氯乙烯的消除似乎呈双指数形式。在单个约束笼中使用相同动物模型进行的研究表明，在气相中“仅头部”暴露于高达7000 ppm的氯乙烯浓度下，摄取同样迅速，随后在数小时的暴露过程中血药浓度达到平稳状态。从氯乙烯环境中移出后，2小时后血液水平迅速下降至几乎检测不到的浓度。描述氯乙烯从血液中分布和消除速率的精确动力学系数也通过静脉注射水性或植物油溶液后获得的血药浓度数据来确定。
