Polyurethanes (PU) are polymers made with diisocyanates such as MDI (4,4'-methylene diphenyl diisocyanate) and TDI (2,4-toluene diisocyanate and 2,6-toluene diisocyanate). Investigations have been undertaken with MDI and TDI to assess dermal uptake and resulting systemic exposure. Absorption, distribution and excretion of MDI was studied in rats using a single dermal administration of (14)C-MDI dissolved in acetone at nominal 165 mg/kg body weight and 15 mg/kg bw (4.0 and 0.4 mg/cm(2)) and intradermal injection of (14)C-MDI dissolved in corn oil at nominal 1.4 mg/kg bw. Dermal absorption of (14)C-MDI (at both doses) was low; at or below 1% of the applied dose. Considerable amounts of the applied radioactivity were found at the application site which could not be washed off. By intradermal administration of (14)C-MDI approximately 66% of applied radioactivity remained at the application site with approximately 26% recovered in excreta, cage wash, tissues and carcass. The absorption, distribution and excretion of 2,4-TDI was studied in rats following a single dermal administration of radiolabelled (14)C-2,4-TDI at nominal 350 mg/kg body weight (12 mg/cm(2)). Dermal absorption of (14)C-2,4-TDI was at or below 1% of the applied dose. Considerable amounts of the applied radioactivity were found at the application site which could not be washed off. In summary the results show that dermal uptake of MDI and TDI is very low. Due to the chemical reactivity of isocyanates it can be expected that small amounts which might be absorbed will react with tissue constituents directly at the exposed skin area, or will be converted to adducts with biomacromolecules or to biologically inactive oligoureas. Overall it is concluded that, following dermal exposure to MDI and TDI, systemic exposures and resulting toxicity, other than the known sensitization, can be expected to be very low. In addition studies were performed with dermal application of unlabelled 2,4 and 2,6 TDI to check the availability and fate of this chemical on rat skin surface and to assess possible tissue damage. These experiments showed that unchanged test material can be detected on rat skin for up to 8h if not washed off. Dermal treatment with 2,4 or 2,6 TDI was associated with irritation with increased severity over a 48 h period after washing with a decontaminant solution.

译文

聚氨酯 (PU) 是用二异氰酸酯如MDI (4,4 '-亚甲基二苯基二异氰酸酯) 和TDI (2,4-甲苯二异氰酸酯和2,6-甲苯二异氰酸酯) 制备的聚合物。已经对MDI和TDI进行了调查,以评估皮肤摄取和由此产生的全身暴露。吸收,在大鼠中研究了MDI的分布和排泄,使用 (14)C-MDI溶解在丙酮中的名义165 mg/kg体重和15 mg/kg体重 (4.0和0.4 mg/cm(2)) 和皮内注射 (14)C-MDI溶解在名义1.4 mg/kg bw的玉米油中。(14)C-MDI (在两种剂量下) 的皮肤吸收低; 处于或低于所施加剂量的1%。在施用部位发现了大量的放射性,无法洗掉。通过皮内施用 (14)C-MDI,大约66% 施加的放射性留在施用部位,大约26% 在排泄物、笼洗、组织和胴体中回收。在大鼠中以标称350 mg/kg体重 (12 mg/cm(2)) 单次皮肤施用放射性标记的 (14)C-2,4-TDI后,研究了2,4-tdi的吸收,分布和排泄。(14)C-2,4-TDI的皮肤吸收处于或低于施加剂量的1%。在施用部位发现了大量的放射性,无法洗掉。总而言之,结果表明,MDI和TDI的皮肤吸收非常低。由于异氰酸酯的化学反应性,可以预期可能被吸收的少量将直接与暴露的皮肤区域的组织成分反应,或者将转化为具有生物大分子的加合物或转化为具有生物活性的寡聚体。总体而言,得出的结论是,在皮肤暴露于MDI和TDI之后,除已知的致敏作用外,全身暴露和由此产生的毒性可望非常低。此外,还进行了皮肤应用未标记2,4和2,6 TDI的研究,以检查这种化学物质在大鼠皮肤表面的可用性和命运,并评估可能的组织损伤。这些实验表明,如果不洗掉,可以在大鼠皮肤上检测到未改变的测试材料长达8小时。在用去污溶液洗涤后的48小时内,用2,4或2,6 TDI进行的皮肤治疗与刺激有关,其严重程度增加。

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