DISTRIBUTION AND REACTIVITY OF INHALED C-14-LABELED TOLUENE DIISOCYANATE (TDI) IN RATS
DISTRIBUTION AND REACTIVITY OF INHALED C-14-LABELED TOLUENE DIISOCYANATE (TDI) IN RATS
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DOI：
10.1007/s002040050094
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发表时间：
1994-07-01
影响因子：
6.1
通讯作者：
BROWN, WE
中科院分区：
文献类型：
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作者：
KENNEDY, AL;WILSON, TR;BROWN, WE
吸入甲苯二异氰酸酯 (TDI) 可导致多种呼吸道疾病。人们担心 TDI 存在潜在的致癌性，因为异氰酸酯在体内水解形成甲苯二胺 (TDA)。长期生物测定（大鼠和小鼠 TDI 吸入与灌胃）的结果是矛盾的，并且在不良反应的解释方面确实存在差异。本研究旨在利用脂肪模型系统中的蒸汽暴露来分析放射性标记 TDI 的分布和反应性。大鼠暴露于浓度范围为 0.026 至 0.821 ppm 的 C-14-TDI 蒸气中 4 小时。所有检查的组织都显示出可检测到的放射性量，其中气道、胃肠系统和血液的放射性水平最高，并且随着暴露浓度的增加而增加。暴露后血流中的放射性浓度与剂量呈线性关系。与血液相关的大部分（74-87%）标记在血浆中回收，其中 97-100% 的 C-14 以生物分子缀合物的形式存在。对胃内容物的分析表明，大部分标签也与高分子量 (>10 kDa) 物种相关。虽然相对于血液而言，较大百分比 (28%) 的标记存在于低分子量部分中，但这种低分子量标记材料代表至少八种不同的成分。因此，在测试的蒸气暴露浓度和时间范围内，似乎缀合是主要反应，并且游离TDA在测试条件下不是主要的体内反应产物。
Inhalation exposure to toluene diisocyanate (TDI) can result in a variety of airway diseases. Concern has been expressed that a putative carcinogenic potential of TDI exists as a result of the formation of toluenediamine (TDA) by hydrolysis of the isocyanate in the body. Results from long-term bioassays (TDI inhalation versus gavage in rats and mice) are contradictory and discrepancies do exist concerning the interpretation of adverse effects. This study was performed to analyze the distribution and reactivity of radioactively-labeled TDI using vapor exposure in a fat model system. Rats were exposed to C-14-TDI vapors at concentrations ranging from 0.026 to 0.821 ppm for 4 h. All tissues examined showed detectable quantities of radioactivity, with the airways, gastrointestinal system and blood having the highest levels which increased with exposure concentration. The concentration of radioactivity in the bloodstream after exposure was linear with respect to dose. The majority (74-87%) of the label associated with the blood was recovered in the plasma, and of this, 97-100% of the C-14 existed in the form of biomolecular conjugates. Analysis of stomach contents shows that the majority of the label is also associated with high (>10 kDa) molecular weight species. While a larger percentage (28%) of the label is found in the low molecular weight fraction relative to blood, this low molecular weight labeled material represents at least eight different components. Thus, over the vapor exposure concentrations and time tested, it appears that conjugation is the predominant reaction and that free TDA is not a primary in vivo reaction product under the conditions tested.