The mitigation of protein glycation in infant formulas can be achieved through the incorporation of antioxidants. Olive mill wastewater phenolic powder (OMW) is a promising dAGEs inhibitor and its inhibitory mechanism varies in different matrices. The addition of OMW to cow-based infant formula resulted in a reduction of up to 34% in dAGEs, while this level reached 48% in soy-based formula. These findings suggest that OMW can be a potential functional ingredient for effectively controlling protein glycation in infant formulas.

Due to new legislation setting maximum limits for non dioxin-like polychlorinated biphenyls (ndl-PCBs), the European Commission Mandate M/523 called for modification of current EN standards for determination of PCBs and organochlorine pesticides (OCPs). This concerns the standards EN-15741:2009 (GC-MS) and EN 15742:2009 (GC-ECD). WFSR (at that time RIKILT) Wageningen University & Research was requested by the European Committee for Standardization (CEN) to adapt current standards. The modifications concern (a) reduction of the limit of quantification (LOQ) for each individual ndl-PCB congener from 5 ng/g to 0.5 ng/g and (b) extending the scope of the methods with the OCPs photoheptachlor, cis/trans nonachlor and keto-endrin. The modifications of EN 15742:2009 (GC-ECD) concern the inclusion of above mentioned additional OCPs. In addition, the determination of the ndl-PCBs is removed from this standard as GC-ECD is not capable of reaching the lowered LOQs for the ndl-PCBs. Therefore, the modified EN 15742:2009 (GC-ECD) limits to the determination of OCPs only. The modifications of EN 15741:2009 (GC-MS(/MS)) concern the inclusion of above mentioned additional OCPs, as well as the lowered LOQs for the ndl-PCBs. The revised standard for GC-ECD (EN15741) could not be evaluated due to insufficient number of participating laboratories (n=3). The extension of the standard with keto-endrin, photo-heptachlor and cis/trans-nonachlor is therefore not possible. Nevertheless the current standard remains intact for the OCPs that were included in the original standard. The standard for GC-MS(/MS) (EN15742) was successfully revised. The method is suitable for analysis of nearly all ndl-PCBs in all tested matrices. The method is also suitable for the majority of OCPs in the included feed matrices. The suitability of the standard could not be evaluated for the newly added organochlorine pesticides (endrin ketone, cis- and trans-nonachlor and photo heptachlor), mainly because only 5 out of 10 laboratories had sent in results and also because some laboratories were non-compliant.

Chlorinated paraffins (CPs) are chemicals used in industries and consumer products in large amounts. These pollutants have been reported in food samples, but data for the Netherlands are missing. The thyroid hormone (TH) system was identified as a target for CPs in rats, but the possible relevance for humans and modes of action related to TH disturbance remained unclear. Given the importance of dietary intake as a main route of human exposure, it is crucial to study the levels of CPs in food samples to allow an assessment of human exposure. The aim of this thesis was to investigate the concentrations of CPs in vegetable oils collected from the Dutch market, including paired crude and refined oils, and to test possible modes of action of potential TH disrupting effects of CPs by studying their effects in selected in vitro assays (new approach methodologies (NAMs)). To put the in vitro results into perspective, they were compared to in vivo internal exposure levels that were estimated using published physiologically based kinetic (PBK) models for rats and humans at defined exposure scenarios. The results revealed that CPs were present in vegetable oils (medium chain CPs were more abundant than short chain CPs). CP levels after refinement were lower than in the related crude oils vegetable oils. Furthermore, CPs, especially the short chain CPs, showed some competition with thyroxine (T4) to bind to TH distributor transthyretin, whereas no competitive binding effects of CPs to T4 were found for the TH distributor thyroxine-binding globulin. CPs were tested for their effects on gene expression in human liver HepaRG cells, all showing to increase mRNA expression of uridine 5'-diphospho-glucuronosyltransferase (UGT) genes responsible for T4 glucuronidation. Short chain CPs were also tested for their ability to increase T4 glucuronidation activity in human liver HepaRG cells, showing and increase in this activity in CP-exposed cells compared to controls. Based on a PBK modelling estimated internal levels of CPs, it was concluded that both TTR binding and UGT induction are likely to play an important role in the thyroid-related effects observed in the reported studies in rats, but not in humans at current CP exposure levels. Altogether, this thesis provided novel data on the occurrence of CPs in vegetable oils in the Netherlands and possible underlying mechanisms of TH disturbance of CPs, contributing to the risk assessment of CPs by using NAMs.