Institute and Outpatient clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Department of Plastic and Hand Surgery, Universitätsklinikum, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Toxicol In Vitro. 2024 Dec;101:105947. doi: 10.1016/j.tiv.2024.105947. Epub 2024 Sep 27.
Technical products containing N-Phenyl-beta-naphthylamine (PBNA) are contaminated with beta-naphthylamine (BNA), a known carcinogen. Both amines penetrate the skin to different degrees, but little is known about their dermal-depot formation. This study investigated the dermal penetration of PBNA and its degradation product BNA using a viable human-skin model. PBNA (259 μg) or BNA (0.52 μg) in n-hexane and industrial grease were applied to freshly excised human skin (n = 6, 0.64 cm) for 2-72 h. After temporary/continuous and single/repeated exposure, samples were taken (stratum corneum, epidermis/dermis, receptor fluid) and analyzed for their amine content by GC-MS. Continuous exposure led to a PBNA dermal depot of ∼47 μg/cm over 72 h. Temporary applications also resulted in lower but consistent PBNA dermal depots. A single 2-h application resulted in a dermal depot of ∼16 μg/cm after 72 h, while this was ∼25 μg/0.64 cm with repeated applications. BNA behaved differently; with repeated 2-h applications, intradermally retained BNA initially increased 3-6 fold, then dropped to ∼200-250 ng/cm. This incomplete decline upon repeated short-term exposure to PBNA suggests that a BNA dermal depot is formed either due to contamination of PBNA with BNA or to enzymatic conversion of PBNA to BNA. Additionally, PBNA dermal depots were saturable under the given conditions. These findings highlight the importance of understanding the dermal-exposure dynamics of potential carcinogenic compounds in industrial settings.
技术产品中含有 N- 苯基-β- 萘胺（PBNA），而该物质会被 β- 萘胺（BNA）污染，BNA 是一种已知的致癌物质。这两种胺都会不同程度地穿透皮肤，但人们对它们在皮肤中的蓄积情况知之甚少。本研究使用活体人类皮肤模型，研究了 PBNA 及其降解产物 BNA 的经皮渗透情况。将 259μg 的 PBNA 或 0.52μg 的 BNA 分别溶于正己烷和工业油脂中，应用于新鲜离体人体皮肤（n=6，0.64cm），接触时间为 2-72h。在临时/连续和单次/重复暴露后，从角质层、表皮/真皮和受体液中取样，并通过 GC-MS 分析其胺含量。连续暴露 72h 后，皮肤中 PBNA 的蓄积量约为 47μg/cm。即使是临时应用，也会导致 PBNA 蓄积量较低但持续存在。单次 2h 暴露后，72h 后皮肤中的 PBNA 蓄积量约为 16μg/cm，而重复应用时约为 25μg/0.64cm。BNA 的行为则不同；重复应用 2h 后，皮内保留的 BNA 最初增加了 3-6 倍，然后降至约 200-250ng/cm。在重复短期接触 PBNA 后，BNA 并未完全下降，这表明 BNA 皮肤蓄积可能是由于 PBNA 被 BNA 污染，也可能是 PBNA 被酶转化为 BNA 所致。此外，在给定条件下，PBNA 皮肤蓄积是可饱和的。这些发现强调了在工业环境中理解潜在致癌化合物经皮暴露动力学的重要性。
