INHALATION TOXICITY STUDIES OF ALPHA,BETA-UNSATURATED KETONES

α、β-不饱和酮的吸入毒性研究

• 批准号: 6289947
• 负责人: DANIEL MORGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289947
• 关键词: environmental toxicology; inhalation drug administration; ketones; saturated /unsaturated bonds; toxicant screening

Methylvinyl ketone (MVK), ethylvinyl ketone (EVK), and 2-cyclohexene-1- one (CHX) were nominated and selected for study by the NTP as part of a class study on alpha,beta-unsaturated ketones. MVK is a representative noncyclic member of the major class of straight-chain aliphatic alpha,beta-unsaturated ketones. EVK is a secondary conjugated carbonyl compound from the subclass of aliphatic alpha,beta-unsaturated ketones. CHX is a prototype of the cyclic alpha,beta-unsaturated ketones. Prechronic Inhalation studies of these ketones were conducted to characterize and compare the relative toxicities and also to facilitate the design of chronic inhalation studies of these chemicals. This chemical class study will allow more accurate prediction of the potential toxicity and carcinogenicity of other untested alpha,beta- unsaturated ketones. Prechronic studies (14- and 90-day) of CHX, MVK and EVK were conducted in B6C3F1 mice and F344 rats. The same study design was used for all three chemicals. In the 90-day studies, rats and mice were exposed to 2.5, 5, and 10 ppm CHX; 0.5, 1, and 2 ppm MVK, and 2, 4, and 8 ppm EVK. Blood and tissue samples were collected and analyzed for changes in clinical pathology, SMVCE, micronucleus assay, and histopathology. All three ketones appeared to be direct-acting irritants and targeted the upper respiratory tract at low exposure concentrations and the upper and lower respiratory tract at higher exposure concentrations. In general MVK was the most toxic and CHX the least toxic. Mice were less sensitive than rats to the toxicity of all three ketones. Histopathological results are still being evaluated for EVK. - alpha,beta-unsaturated ketones, methylvinyl ketone, 2- cyclohexen-1-one, ethylvinyl ketone, inhalation, toxicity

甲基乙烯基酮 (MVK)、乙基乙烯基酮 (EVK) 和 2-环己烯-1-酮 (CHX) 被 NTP 提名并选择进行研究，作为 α,β-不饱和酮类研究的一部分。 MVK 是直链脂肪族 α,β-不饱和酮主要类别中的代表性非环状成员。 EVK 是脂肪族 α,β-不饱和酮亚类的二级共轭羰基化合物。 CHX是环状α,β-不饱和酮的原型。对这些酮进行慢性吸入研究是为了表征和比较相对毒性，并促进这些化学品的慢性吸入研究的设计。这项化学类研究将能够更准确地预测其他未经测试的 α,β-不饱和酮的潜在毒性和致癌性。在 B6C3F1 小鼠和 F344 大鼠中进行了 CHX、MVK 和 EVK 的慢性前研究（14 天和 90 天）。所有三种化学品均采用相同的研究设计。在为期 90 天的研究中，大鼠和小鼠分别暴露于 2.5、5 和 10 ppm CHX； 0.5、1 和 2 ppm MVK，以及 2、4 和 8 ppm EVK。收集血液和组织样本并分析临床病理学、SMVCE、微核测定和组织病理学的变化。所有三种酮似乎都是直接刺激物，在低暴露浓度时针对上呼吸道，在较高暴露浓度时针对上呼吸道和下呼吸道。一般来说，MVK 毒性最强，CHX 毒性最小。小鼠对所有三种酮的毒性不如大鼠敏感。 EVK 的组织病理学结果仍在评估中。 - α，β-不饱和酮，甲基乙烯基酮，2-环己烯-1-酮，乙基乙烯基酮，吸入，毒性