Absorption, distribution, metabolism and excretion of an inhalation dose of [14C] 4,4′-methylenediphenyl diisocyanate in the male rat
Absorption, distribution, metabolism and excretion of an inhalation dose of [14C] 4,4′-methylenediphenyl diisocyanate in the male rat
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DOI：
10.1080/00498250500057591
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发表时间：
2005-03-01
期刊：
影响因子：
1.8
通讯作者：
Shiotsuka, R
中科院分区：
文献类型：
--
作者：
Gledhill, A;Wake, A;Shiotsuka, R
研究了目标浓度为2 mg m（-3）的[C-14]- 4,4′-亚甲基二苯二异氰酸酯（MDI）在雄性大鼠体内吸入6小时后的剂量、组织分布、代谢、途径和排泄率。接受的平均剂量相当于每只动物0.078 mg MDI，其中25%至32%的放射性标记物质可全身获得。放射性分布在所有被检查的组织中，呼吸道和胃肠道中所占比例最高，这表明口服摄入和肺部吸收都对[C-14]-MDI衍生物质的全身剂量有贡献，口服摄入和大部分内部剂量是由暴露后通过修饰皮毛摄入放射性标记物质造成的。放射性主要通过粪便排出（约占接受剂量的80%）。胆汁和尿液的排泄各占剂量的15%以下。MDI在摄取后被广泛代谢，有两条明显的转化途径；提出的自发形成混合分子量聚氨酯和酶催化代谢的系统可用的MDI或MDI衍生物得到n -乙酰化和n -乙酰化羟基化的产品。所有生物基质（尿液、粪便、胆汁）均未检测到游离丙二醛。
The received dose, tissue distribution, metabolism, routes and rates of excretion of [C-14]-4, 4'-methylenediphenyl diisocyanate (MDI) were investigated in the male rat following a 6-h inhalation exposure to [C-14]-MDI at a target concentration of 2 mg m(-3).The mean dose received was equivalent to 0.078 mg MDI per animal, of this between 25 and 32% of radiolabelled material was available systemically. Radioactivity was distributed to all tissues examined with the highest proportions present in the respiratory and gastrointestinal tracts, suggesting that both oral ingestion and pulmonary absorption contributed to the systemic dose of [C-14]-MDI derived material, with the oral ingestion and the majority of the internal dose resulting from ingestion of radiolabelled material by grooming the pelt after exposure. Radioactivity was excreted mainly via faeces ( about 80% of the received dose). Excretion in bile and urine each accounted for less than 15% of the dose. MDI was extensively metabolized after uptake, with two routes of transformation evident; the proposed spontaneous formation of mixed molecular weight polyureas and the enzyme catalysed metabolism of systemically available MDI or MDI derivatives to give N-acetylated and N-acetylated hydroxylated products. No free MDA was detected in any of the biomatrices ( urine, faeces, bile) investigated.