Mineral oils are widely applied in food production and processing and may contain polycyclic aromatic hydrocarbons (PAHs). The PAHs that may be present in mineral oils are typically alkylated, and have been barely studied. Metabolic oxidation of the aromatic ring is a key step to form DNA-reactive PAH metabolites, but may be less prominent for alkylated PAHs since alkyl substituents would facilitate side chain oxidation as an alternative. The current study investigates this hypothesis of preferential side chain oxidation at the cost of aromatic oxidation using naphthalene and a series of its alkyl substituted analogues as model compounds. The metabolism was assessed by measuring metabolite formation in rat and human liver microsomal incubations using UPLC and GC-MS/MS. The presence of an alkyl side chain markedly reduced aromatic oxidation for all alkyl-substituted naphthalenes that were converted. 1-n-Dodecyl-naphthalene was not metabolized under the experimental conditions applied. With rat liver microsomes for 1-methyl-, 2-methyl-, 1-ethyl-, and 2-ethyl- naphthalene, alkyl side chain oxidation was preferred over aromatic oxidation. With human liver microsomes this was the case for 2-methyl-, and 2-ethyl-naphthalene. It is concluded that addition of an alkyl substituent in naphthalene shifts metabolism in favor of alkyl side chain oxidation at the cost of aromatic ring oxidation. Furthermore, alkyl side chains of 6 or more carbon atoms appeared to seriously hamper and reduce overall metabolism, metabolic conversion being no longer observed with the C12 alkyl side chain. In summary, alkylation of PAHs likely reduces their chances of aromatic oxidation and bioactivation.

中文翻译：

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人和大鼠肝脏微粒体通过烷基侧链或芳香族氧化作用进行萘及其烷基化同源物的体外代谢。

矿物油广泛用于食品生产和加工中，并且可能包含多环芳烃（PAH）。矿物油中可能存在的PAH通常是烷基化的，并且尚未进行过研究。芳环的代谢氧化是形成DNA反应性PAH代谢产物的关键步骤，但对于烷基化PAH可能不那么重要，因为烷基取代基可以促进侧链氧化。当前的研究以萘和一系列烷基取代的类似物为模型化合物，以芳香族氧化为代价，研究了优先侧链氧化的假设。通过使用UPLC和GC-MS / MS测量大鼠和人肝脏微粒体温育物中代谢物的形成来评估代谢。烷基侧链的存在显着降低了所有被烷基取代的萘的芳族氧化。1-n-十二烷基萘在应用的实验条件下不会代谢。对于用于1-甲基，2-甲基，1-乙基和2-乙基萘的大鼠肝微粒体，烷基侧链氧化优于芳族氧化。对于人类肝脏微粒体，2-甲基萘和2-乙基萘就是这种情况。可以得出结论，在萘中添加烷基取代基会以芳香环氧化为代价，使新陈代谢向烷基侧链氧化转移。此外，具有6个或更多个碳原子的烷基侧链似乎严重阻碍并降低了整体代谢，在C 12烷基侧链中不再观察到代谢转化。总之，