Abstract
Alkyl-substituted PAHs may be present in certain petroleum-derived products and in the environment and may eventually end up in consumer products, such as foodstuffs, cosmetics and pharmaceuticals. Safety concerns over possible exposure to alkylated PAHs have emerged. Bioactivation is a prerequisite for the mutagenicity and carcinogenicity of PAHs and has been extensively studied for non-substituted PAHs, while data on the bioactivation of alkyl-substituted PAHs are scarce. The present study investigated the effect of alkyl substitution on the CYP 450-mediated metabolism of phenanthrene and eight of its alkylated congeners by quantifying metabolite formation in rat and human liver microsomal incubations. Furthermore, the mutagenicity of four selected methylated phenanthrenes was compared to that of phenanthrene using the Ames test. The obtained results support the hypothesis that alkyl substitution shifts the oxidative metabolism from the aromatic ring to the alkyl side chain. Increasing the length of the alkyl chain reduced overall metabolism with metabolic conversion for 1-n-dodecyl-phenanthrene (C12) being negligible. 1- and 9-methyl-phenanthrene, in which the methyl group generates an additional bay region-like structural motif, showed mutagenicity toward Salmonella typhimurium TA98 and TA 100, whereas phenanthrene and also 2- and 3-methyl-phenanthrene, without such an additional bay region-like structural motif, tested negative. It is concluded that the position of the alkylation affects the metabolism and resulting mutagenicity of phenanthrene with the mutagenicity increasing in cases where the alkyl substituent creates an additional bay region-like structural motif, in spite of the extra possibilities for side chain oxidation.
Highlights
The unintentional consumption of polycyclic aromatic hydrocarbons (PAHs) via contaminated food is a general food safety issue
The consumption of food contaminated with petrogenic polycyclic aromatic hydrocarbons (PPAHs) from petroleum-derived products or environmental sources may be of concern to human health
Since data on the metabolic fate of most PPAHs, in particular alkylated PAHs, are lacking, the microsomal oxidative metabolism, likely mediated by cytochrome P450 enzymes, of phenanthrenes with various types of alkylation was studied to investigate the effect of the alkyl substitution
Summary
The unintentional consumption of polycyclic aromatic hydrocarbons (PAHs) via contaminated food is a general food safety issue. The PAHs present in food are typically unsubstituted as they are pyrogenic in nature, formed by incomplete heating or combustion of organic matter (EFSA 2008). Contamination of food with petrogenic polycyclic aromatic hydrocarbons (PPAHs), which are typically alkylated, is an emerging health concern (EFSA 2012; Fengler and Gruber 2020; Grob 2018; Pirow et al 2019; Van Heyst et al 2018). In spite of the fact that petroleum-derived mineral oils are highly refined to eliminate. Archives of Toxicology (2022) 96:1109–1131 Bay region CYP450 10 * * * *.
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