DISPOSITION OF HEXABROMONAPHTHALENE

六溴萘的处置

• 批准号: 3965182
• 负责人: L S BIRNBAUM
• 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/3965182
• 关键词: biotransformation; bromine; chemical structure function; cleft palate; congenital kidney disorder; dosage; environmental toxicology; fire prevention; gastrointestinal toxin absorption; halobiphenyl /halotriphenyl compound; liver metabolism; naphthalenes; nuclear magnetic resonance spectroscopy; toxicant screening; toxin metabolism

Bromonapthalenes have no known industrial use or application, but have been identified as contaminants of Firemaster BP-6, the toxic mixture of polybrominated biphenyls used as a fire retardant and involved in a major episode of environmental poisoning in Michigan. Structurally related to other halogenated aromatic xenobiotics, their toxicity and disposition seem to vary with the position of bromination. This work has studied the chemical disposition of a mixture of 2 hexabromonapthalenes (HBNs), previously identified as a single isomer, 1,2,3,4,6,7-HBN. The compound is incompletely absorbed after an oral dose. After iv treatment over 50% of the dose is excreted as metabolites within 3 days. However, the remainder of the dose seems to be extremely persistent, over 25% remaining in the liver after 35 days. These disposition results led to proof of the presence of two isomers by high resolution NMR, present in a ratio of 65:35 which have been identified as 1,2,3,4,6,7- and 2,3,4,5,6,7 -HBN. The difference in the fate of the two isomers has been proven by isolation and characterization by high resolution NMR of the HBN remaining in the liver 10 days after treatment. While the HBN dosed was in an isomeric ratio of 65:35 (1,2,3,4,6,7-:2,3,4,5,6,7-), the HBN in the liver 10 days after oral treatment was in the ratio of 20:80. The toxicity of this HBN mixture was examined in mice. A single oral dose as high as 1000 mg/kg had no toxic effects. However, repeat dose toxicity was detected at doses as low as 5 mg/kg for 7 days. The toxic response was toxicity similar to that seen for TCDD and related compounds. A complete teratology study was carried out and the teratogenic response was identical to that observed with TCDD, with the main endpoints being kidney anomalies and cleft palate at doses as low as 1 mg/kg.

溴萘没有已知的工业用途或应用，但已被 被鉴定为 Firemaster BP-6 的污染物，有毒混合物 多溴联苯用作阻燃剂并涉及主要 密歇根州发生环境中毒事件。 结构上相关 其他卤代芳香族异生物质，其毒性和处置似乎 随溴化位置的变化而变化。 这项工作研究了 2 种六溴萘 (HBN) 混合物的化学处置， 先前被鉴定为单一异构体，1,2,3,4,6,7-HBN。 该化合物是 口服剂量后吸收不完全。 静脉注射治疗后超过 50% 剂量在3天内作为代谢物排出体外。 然而，剩余的 剂量似乎极其持久，超过 25% 残留在体内 35天后肝脏。 这些处置结果证明了 高分辨率 NMR 表明存在两种异构体，比例为 65:35 已被鉴定为1,2,3,4,6,7-和2,3,4,5,6,7-HBN。 这 两种异构体的命运差异已通过分离和 通过高分辨率 NMR 表征肝脏中残留的 HBN 治疗后10天。 虽然所添加的 HBN 的异构体比例为 65:35 (1,2,3,4,6,7-:2,3,4,5,6,7-)，口服10天后肝脏中的HBN 治疗比例为20：80。 该 HBN 混合物的毒性为 在小鼠身上进行了检查。 单次口服剂量高达 1000 mg/kg 无毒性 影响。 然而，在低至 5 剂量时检测到重复剂量毒性。 毫克/公斤，持续7天。 毒性反应与所见的毒性相似 TCDD 及相关化合物。 进行了完整的畸形学研究 致畸反应与 TCDD 观察到的结果相同， 主要终点是低剂量时的肾脏异常和腭裂 为 1 毫克/千克。