title: Dermale Aufnahme aromatischer Amine unter simulierten Arbeitsplatzbedingungen
Creators: name: Baierl, Moritz
Publisher: name: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Year: 2024

description: Objectives The aromatic amines N-phenyl-2-naphthylamine (P2NA) and 2-naphthylamine (2NA) have been part of occupational medical examinations for some time (BK-Report, 2019). P2NA in particular was widely used as an antioxidant in lubricating greases and was for a long time an integral part of the daily handling of contact substances for industrial workers. However, P2NA was not present in its pure form in the corresponding industrial products, but was contaminated with 2NA to a certain degree (BK-Report, 2019). A high risk for the development of urothelial carcinomas has been proven for 2NA, so that there is interest in researching the exposure to these substances in everyday work life (BK-Report, 2019. Weiss et al., 2013). It is known that both substances can penetrate into the skin to a certain extent, but little is known about any cutaneous depot formation or percutaneous penetration (Dennerlein et al., 2017). The aim of our project was to investigate dermal uptake and dermal absorption under everyday exposure scenarios over a period of 72 hours. Design and Methods Due to its high correlation with in vivo experiments an in vitro setting using the Franz chamber system was applied (Lehman et al., 2011). In the experiment the aromatic amines 2NA and P2NA were applied in concentrations of 0.52 μg/0.64 cm2 and 259 μg/0.64 cm2 one time or repeatedly to a fresh human skin obtained by abdominal plastic surgery and prepared to a thickness of 0,9 mm. The amines were left on the skin for 2-72 h, depending on the setting. After the corresponding exposure periods the surfaces were cleaned with the help of cotton swaps. The depot formation was analyzed by samples from "tape strips" and skin punches, the percutaneous penetration through regular analyses of the subcutaneous albumin solution. The evaluation was carried out by the use of gas chromatography (GC) and mass spectrometry (MS) . Observations and Results In the case of P2NA percutaneous penetration started with a delay, extending till the end of the test period of 72 hours. A cutaneous depot formation was proved; depending on the setting, it stabilized at different values until the end of the test after 72 hours, but showed saturation at around 47 μg/ cm2. Percutaneous penetration was also found for 2NA, but it was more rapid than for P2NA; depot formation could also be observed. Saturation was not recognizable, but after repetitive application a strong temporary increase in the depot values with a consecutive decrease was noticeable. However, this did not reach the previous initial value, so that an accumulation can be assumed. Concerning the question if an intracutaneous metabolism of P2NA to 2NA is likely, our results show, that this seems possible. Conclusions The synopsis of the results shows that percutaneous penetration and dermal depot formation take place over an extended period beyond the actual application. As a result, a systemic uptake and consequently a health-endangering potential of the investigated aromatic amines (AA) can be assumed under real and daily working conditions. The results can serve as a basis for further studies with a longer test duration on the question of which exact amounts of AA are absorbed into the body or are newly formed there through local metabolism. This could contribute to the determination of a critical, cumulative and health-endangering dose of P2NA and 2NA in the context of work-related exposure and thus to the acknowledgment as an occupational disease as well as to its avoidance.