DISPOSITION OF HEXABROMONAPHTHALENE

溴并没有已知的工业用途或用途，但已经 被确认为消防主BP-6的污染物，有毒混合物 多溴联苯用作阻燃剂，并涉及一种主要的 密歇根州发生环境中毒事件。在结构上与…有关 其他卤代芳香族异物的毒性和处置 随着溴化位置的不同而变化。这项工作研究了 化学处理2种六溴单萘(HBN)的混合物， 以前确定为单一异构体，1，2，3，4，6，7-HBN。该化合物是 口服后吸收不完全。静脉注射治疗后50%以上 该剂量在3天内以代谢物的形式排出。然而，其余的 的剂量似乎非常持久，超过25%的人留在 35天后取肝组织。这些处置结果导致了 高分辨核磁共振显示存在两种异构体，以65：35的比例存在 已鉴定为1，2，3，4，6，7-和2，3，4，5，6，7-HBN。这个 两种异构体命运的差异已被分离和验证 高分辨核磁共振表征残留在肝脏中的HBN 治疗后10天。而剂量的HBN的异构化比率为 65：35(1，2，3，4，6，7-：2，3，4，5，6，7-)，口服10天后肝脏内HBN 治疗比例为20：80。这种HBN混合物的毒性是 在小鼠身上进行了检查。单次口服1000毫克/公斤没有毒性。 效果。然而，在低至5%的剂量下检测到重复剂量的毒性。 Mg/kg，连续7天。毒性反应与所见的毒性相似。 TCDD及相关化合物。进行了完整的畸胎学研究 致畸反应与TCDD观察到的相同， 低剂量的主要终点是肾脏异常和腭裂 为1 mg/kg。

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.