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首页> 外文期刊>Archives of Toxicology >Quantification of N -phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions
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Quantification of N -phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions

机译:通过气相色谱法和同位素稀释质谱法定量N-苯基-2-萘胺及其在工作场所条件下的经皮吸收exvivo

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Abstract N -Phenyl-2-naphthylamine (P2NA) is an antioxidant used to protect rubbers from flex-cracking. P2NA can be converted in vivo to 2NA, one of the most potent bladder carcinogens. Here, we report the specific and ultra-sensitive quantification of P2NA in the receptor fluid of Franz diffusion cells by gas chromatography and isotope-dilution tandem-mass spectroscopy (GC–MS/MS). The experimental conditions were optimized to minimize losses of P2NA due to surface absorption on glass, plastic, and rubber material, and subsequently validated. Static and dynamic diffusion cell conditions were used to study the percutaneous penetration of P2NA into freshly prepared porcine skin. The experimental settings closely resembled those of the printing industry in the 1960s/1970s in Germany where P2NA-containing solutions in dichloromethane have been used. P2NA penetrated the skin at very low levels (0.02 ± 0.01?μg/cm 2 /h) with a cumulative penetrated amount of 0.80 ± 0.26?μg/cm 2 , a lag time of 6.33 ± 2.21?h and under dynamic conditions. Compared to the receptor fluid, 10–40-fold higher concentrations were found in the skin, predominantly in the dermis and the stratum corneum. Dichloromethane acted as a penetration enhancer by increasing the cumulative penetrated amounts and the recovery of P2NA in both the receptor fluid and the skin, while shortening its lag time. However, the flux remained unaffected. Due to its accumulation in subcutaneous layers, we finally proved that P2NA is continuously released into the receptor fluid despite exposure cessation up to 160?h. Overall, the results show that close attention has to be paid to dermal absorption of P2NA in exposed workers.
机译:摘要N-苯基-2-萘胺(P2NA)是一种用于保护橡胶免受弯曲开裂的抗氧化剂。 P2NA可以在体内转化为2NA,其中一个最有效的膀胱致癌致癌物。在此,我们通过气相色谱和同位素稀释串联体谱(GC-MS / MS)报告Franz扩散细胞的受体流体中P2NA的特异性和超敏感量化。优化实验条件以最小化由于玻璃,塑料和橡胶材料上的表面吸收而最小化P2NA的损耗,随后验证。静态和动态扩散细胞条件用于研究P2NA的经皮渗透到新鲜制备的猪皮肤中。实验设置在德国的20世纪60年代/​​ 70年代印刷行业的实验设置非常类似于含有P2NA的二氯甲烷的溶液。 P2NA以极低的水平(0.02±0.01×μg/ cm 2 / h)穿透皮肤,累积渗透量为0.80±0.26ΩΩ×μg/ cm 2,延迟时间为6.33±2.21Ω,在动态条件下。与受体流体相比,皮肤中发现10-40倍的浓度,主要在真皮和角质层中。通过增加受体流体和皮肤中的累积渗透量和P2NA的恢复,二氯甲烷作为渗透增强剂,同时缩短其滞后时间。然而,助焊剂保持不受影响。由于其在皮下层的积累,我们最终证明P2NA虽然暴露于160μl,但是尽管暴露在接触液体,但是P2NA连续释放到受体流体中。总体而言,结果表明,必须对暴露工人的P2NA皮肤吸收的密切关注。

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