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单次和多次暴露于恒定剂量氯乙烯单体后的癌症诱发情况。

Cancer induction following single and multiple exposures to a constant amount of vinyl chloride monomer.

作者信息

Hehir R M, McNamara B P, McLaughlin J, Willigan D A, Bierbower G, Hardisty J F

出版信息

Environ Health Perspect. 1981 Oct;41:63-72. doi: 10.1289/ehp.814163.

Abstract

Vinyl chloride monomer (VCM), already identified as a human animal carcinogen, was selected as a model agent to explore an area of concern for single and intermittent low level exposure. In traditional cancer bioassay, animals are repeatedly exposed over their lifespan to a dose of suspected chemical. In the current studies rats and mice were exposed in an inhalation chamber to single one-hour doses of VCM ranging from 50 to 50,000 ppm. A second group was given 10 one-hour exposures to 500 ppm or 100 one-hour exposures to 50 ppm of the same chemical. All animals were then observed for the remainder of their lives, generally 18-24 months. Moribund animals were euthanized, and survivors were sacrificed on schedule and their tissues examined for pathological changes. Specifically, the oncogenic study demonstrated dose related effects for single one-hour exposure of VCM at high levels, i.e., 5,000 and 50,000 ppm. These concentrations increased the incidence of pulmonary adenomas and carcinomas in mice. Repeated exposure of A/J mice to the same chemical at 500 ppm X 10 one-hour exposures also increased the incidence of pulmonary adenomas and carcinomas which are considered highly one-hour exposure, no significant increase in tumors was observed. Rats exposed to identical concentrations of VCM failed to elicit a tumorigenic response.

摘要

氯乙烯单体(VCM)已被确认为人类和动物致癌物,被选作一种模型物质,以探究单次和间歇性低水平暴露所涉及的一个问题领域。在传统的癌症生物测定中,动物在其整个生命周期内反复接触一定剂量的可疑化学物质。在当前的研究中,大鼠和小鼠在吸入舱中暴露于单次一小时剂量的VCM,剂量范围为50至50,000 ppm。第二组动物接受了10次一小时的500 ppm VCM暴露,或100次一小时的50 ppm相同化学物质暴露。然后对所有动物的余生进行观察,通常为18 - 24个月。濒死的动物实施安乐死,存活的动物按计划处死,并对其组织进行病理变化检查。具体而言,致癌性研究表明,单次一小时的高水平VCM暴露(即5,000和50,000 ppm)存在剂量相关效应。这些浓度增加了小鼠肺腺瘤和癌的发生率。将A/J小鼠反复暴露于500 ppm的相同化学物质下10次一小时,也增加了肺腺瘤和癌的发生率,而被认为是高度致癌的单次一小时暴露,则未观察到肿瘤有显著增加。暴露于相同浓度VCM的大鼠未引发致瘤反应。

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