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Thomas Bruning – 1st expert on this subject based on the ideXlab platform
Metabolic dephenylation of the rubber antioxidant N-phenyl-2–Naphthylamine to carcinogenic 2–Naphthylamine in ratsArchives of Toxicology, 2013Co-Authors: Tobias Weiss, Hermann M Bolt, Gerhard Schlüter, Stephan Koslitz, Dirk Taeger, Peter Welge, Thomas BruningAbstract:
N -Phenyl-2–Naphthylamine (P2NA) was widely used as oxidation inhibitor, particularly in rubber manufacturing. Technical-grade P2NA was contaminated with carcinogenic 2–Naphthylamine (2NA), and bladder cancer risk in exposed workers was attributed to this impurity. Investigations in humans and mammalian species revealed that small amounts of 2NA are excreted into urine after exposure to P2NA. However, since 2NA per se is not carcinogenic and main downstream metabolites of 2NA have not been found in urine so far, it remained uncertain if 2NA derived from P2NA dephenylation is further activated to carcinogenic downstream metabolites. An experimental animal study was therefore designed to indicate if, and if yes to which extent, 2NA from P2NA dephenylation is accessible to the metabolic pathway that is held responsible for the carcinogenicity of 2NA. Groups of 5 male and female CD rats were dosed with P2NA (2–550 mg/kg b.w.) and 2NA (0.075–75 mg/kg b.w.); 2NA-haemoglobin adducts and urinary 2NA excretion were determined applying GC–MS/MS. 2NA haemoglobin adducts originated dose-dependently after 2NA and P2NA dosing. To induce identical adduct concentrations, an approximately 100–200-fold higher dose of P2NA was necessary compared to 2NA. Since haemoglobin adducts are formed by the same pathway ( N -hydroxylation) as the ultimate carcinogens from 2NA, the comparison of adduct concentrations after 2NA and P2NA dosage permits a quantitative estimate of the carcinogenicity of P2NA. The results show that 2NA derived from dephenylation of P2NA enters the carcinogenic downstream pathway of 2NA in rats. Hence, the bladder cancer risk after human exposures to P2NA must be re-evaluated.
dephenylation of the rubber chemical n phenyl 2 Naphthylamine to carcinogenic 2 Naphthylamine a classical problem revisitedCritical Reviews in Toxicology, 2007Co-Authors: Tobias Weiss, Thomas Bruning, Hermann M BoltAbstract:
N-Phenyl-2–Naphthylamine (PBNA) represents an example of a suspected carcinogen that is found negative in mutagenicity and clastogenicity testing as well as in long-term animal carcinogenicity bioassays in several species, but for which a carcinogenic risk cannot be excluded because of its metabolic conversion to the known human carcinogen 2–Naphthylamine. Also, epidemiologic studies failed to indicate an elevated bladder cancer risk in humans occupationally exposed to PBNA. The amounts of 2–Naphthylamine found in the urine of different species including humans after exposure to PBNA indicate unequivocally that PBNA is dephenylated to some extent. These are not explained by the 2–Naphthylamine impurities in technical-grade PBNA. To explain the metabolic dephenylation process, it has been suggested that PBNA is metabolized by cytochrome P-450 (CYP) enzymes to the phenolic derivative 4′-hydroxy-N-phenyl-2–Naphthylamine, followed by its further oxidation to the quinone imine, which subsequently hydrolyses to…
Ling Song – 2nd expert on this subject based on the ideXlab platform
studies on the toxic interaction mechanism between 2 Naphthylamine and herring sperm dnaJournal of Biochemical and Molecular Toxicology, 2013Co-Authors: Ling SongAbstract:
The toxic interaction between 2–Naphthylamine (2-NA) and herring sperm deoxyribonucleic acid (hs-DNA) has been thoroughly investigated by UV absorption, fluorescence, and circular dichroism (CD) spectroscopic methods. UV absorption result indicates that 2-NA may intercalate into the stack base pairs of DNA during the toxic interaction of 2-NA with DNA. A fluorescence quenching study shows that DNA quenches the intrinsic fluorescence of 2-NA via a static pathway. The studies on effects of ionic strength and anionic quenching rule out electrostatic and groove bindings as the dominant binding modes. Further studies on denatured DNA fluorescence quenching and thermal melting studies confirm that the dominant binding mode of 2-NA-DNA is intercalative binding. A CD spectral study shows that the binding interaction of 2-NA with DNA leads to the disorganization of the neat double-helical structure of hs-DNA. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:279-285, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21488
spectroscopic investigation of the interaction of the toxicant 2 Naphthylamine with bovine serum albuminJournal of Biochemical and Molecular Toxicology, 2011Co-Authors: Mingmao Chen, Guangling Bian, Ling SongAbstract:
The mechanism of interaction between bovine serum albumin (BSA) and 2–Naphthylamine (2-NA) in aqueous solution was investigated by fluorescence spectroscopy, circular dichroism (CD) spectra, and UV–vis spectroscopy. It was proved from fluorescence spectra that the fluorescence quenching of BSA by 2-NA was a result of the formation of complex between 2-NA and BSA, and the binding constants (Ka) as well as the numbers of binding sites for 2-NA in BSA were determined according to the modified Stern–Volmer equation. The results of synchronous fluorescence and CD spectra demonstrated 2-NA could decrease the amount of α-helix of BSA, leading to the loosening of protein skeleton. UV–vis spectroscopy and resonance light scattering spectra (RLS) results also suggested the conformation of BSA were changed and the BSA aggregation occured, which could induce toxic effects on the organism. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:362–368 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20400
N G Kozlov – 3rd expert on this subject based on the ideXlab platform
Reaction of 2′-hydroxy[1,1′;3′,1″]terphenyl-5′-carbaldehyde with 2–Naphthylamine and 1,3-diketonesRussian Journal of Organic Chemistry, 2020Co-Authors: N G Kozlov, V. A. Tarasevich, D. A. Vasilevskii, L I BasalaevaAbstract:
The condensation of 2′-hydroxy[1,1′;3′,1″]terphenyl-5′-carbaldehyde with 2–Naphthylamine and 1,3-cyclohexanedione or dimedone gave 7,8,9,10,11,12-hexahydrobenzo[a]acridin-11-ones, while analogous three-component condensation with 1,3-indandione afforded azaindeno[1,2-b]phenanthren-12-one. In addition, hexahydro-2H-xanthene-1,8-diones and arylmethylenebisdiketones were isolated as by-products.
condensation of 2 Naphthylamine or n benzyl 2 Naphthylamines with formaldehyde and methyl 2 2 dimethyl 4 6 dioxocyclohexane 3 carboxylateRussian Journal of Organic Chemistry, 2012Co-Authors: N G Kozlov, A P Kadutskii, A V BaranovskiiAbstract:
Condensation of 2–Naphthylamine with formaldehyde and methyl 2,2-dimethyl-4,6-dioxocyclohexanecarboxylate afforded depending on the reaction conditions methyl 9,9-dimethyl-11-oxo-8,9,10,12-tetrahydro-7H-benzo[a]acridine-10-carboxylate or 4-alkoxymethyl-1,4-dihydro-2′,6′-dioxo-4′,4′-dimethyl-2′H,3H,6′Hspirobenzo[f]quinoline-2,1′-cyclohexyl-3′-carboxylate. The condensation of N-benzyl-2–Naphthylamines with formaldehyde and methyl 2,2-dimethyl-4,6-dioxocyclohexanecarboxylate provided with the quantitative yield the corresponding methyl 4-benzyl-1,4-dihydro-2′,6′-dioxo-4′,4′-dimethyl-2′H,3H,6′H-spirobenzo[f]quinoline-2,1′-cyclohexyl-3′-carboxylates.
cascade heterocyclization of 2 Naphthylamine with substituted benzaldehydes and acetophenonesRussian Journal of General Chemistry, 2006Co-Authors: N G Kozlov, L I BasalaevaAbstract:
Cascade heterocyclization of 2–Naphthylamine with substituted benzaldehydes and acetophenones gave 1,3-diarylbenzo[f]quinoline derivatives in which the aldehyde fragment resides on C1, and acetophenone fragment, on C3.