Quantification of N-phenyl-2-naphthylamine by gas chromatography and isotope-dilution mass spectrometry and its percutaneous absorption ex vivo under workplace conditions

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/cm2/h) with a cumulative penetrated amount of 0.80 ± 0.26 µg/cm2, 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-017-2046-2) contains supplementary material, which is available to authorized users.

Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model

“…For halogenated flame retardants, adherence was not a problem in the same system (Frederiksen et al, 2016). Marek et al (2017) reported that adherence of n-phenyl-2-naphtylamine (log K ow of 4.4) was highly dependent on the receptor fluid; adding 5% bovine serum albumin to the receptor fluid, as it was done in the current study, markedly reduced the adherence to the glass surfaces in the receptor chamber.…”

Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry: A Strategy for Optimization, Characterization, and Quantification of Antioxidant Nitro Derivatives

“…N -Phenyl-β-naphthylamine (PBNA) is a widely used antioxidant in numerous industrial applications, such as the manufacture of rubber, plastic, dyes, various greases, lubricating and transformer oils, and energetic materials. − In the presence of oxidative or hydrolyzing agents such as oxygen, nitrogen oxides (NO x ), and nitrous and nitric acids (HNO x ), this secondary arylamine stabilizer can effectively protect energetic materials from oxidation or hydrolysis by scavenging the free radicals (e.g., NO 2 radical) and hence reducing the acidity. ,,,, In a similar class of antioxidants (e.g., diphenylamine and triphenylamine), nitration of arylamines generally forms nitro derivatives by reacting with nitrogen oxide radicals − ,− and can be characterized using mass spectrometry (MS) through rationalization of fragmentation . Accordingly, PBNA can also form mononitro derivatives when it undergoes similar reactions.…”

Determination of phenyl(2-naphthyl)amine concentrations in the working environment air using HPLC-FLD technique

“…Narażenie zawodowe na FNA występuje głównie przez układ oddechowy i skórę [4][5][6]. W wyniku zatrucia ostrego FNA w postaci pyłu może wystąpić kaszel, zaczerwienienie spojówek, łzawienie oczu, ból głowy, duszności, zaburzenia świadomości, utrata przytomności i zgon.…”