The effects of alkyl substitution on metabolism and resulting toxicities of Polycyclic Aromatic Hydrocarbons (PAHs) that may be present in mineral oils

Research output: Thesisinternal PhD, WU

Abstract

Mineral oil aromatic hydrocarbons (MOAH) have been presented as a modern emerging food safety concern by the European Food Safety Authority (EFSA). MOAH is defined as a chromatographic fraction in the analysis of mineral oil hydrocarbons (MOH) in food and does not represent well defined substances or mixtures. The sources of foodborne MOAH include environmental contamination and intentional uses of mineral oils in consumer products or production processes. Some non-substituted PAHs are known to be genotoxic carcinogens and have been extensively studied, however the majority of the compounds represented by MOAH are highly alkylated aromatic hydrocarbons for which the toxicological data are scarce. Potential concerns for genotoxicity, carcinogenicity and developmental toxicity upon MOAH exposure have been raised. However, the lack of toxicological data on related alkyl substituted polycyclic aromatic hydrocarbons (PAHs) seriously hampers a proper hazard assessment and therefore challenges the risk assessment of MOAH.

The present thesis aims at (1) providing data on oxidative metabolism and resulting toxicities of a series of the selected non-substituted and alkyl-substituted aromatic hydrocarbons using in vitro assays and (2) developing a physiologically-based kinetic (PBK) modeling- facilitated quantitative in vitro-in vivo-extrapolation (QIVIVE) approach for prediction of in vivo toxicity of selected PAH. The latter is needed to define data for risk assessment as a proof of principle for using new approach methodologies (NAMs). It was hypothesized (1) that alkylated PAHs will be metabolized preferably on the alkyl side chain rather than on the condensed aromatic rings which can be expected to facilitate their excretion rather than their bioactivation to potentially DNA-reactive metabolites, and (2) that the presence of an additional bay region like aromatic motif introduced by methyl substitution may affect the genotoxic potential of the PAHs.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Rietjens, Ivonne, Promotor
  • Boogaard, Peter, Promotor
Award date28 Feb 2022
Place of PublicationWageningen
Publisher
Print ISBNs9789464470499
DOIs
Publication statusPublished - 2022

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