Compounds in food packaging materials - toxicological profiling of knowns and unknowns

Food contact materials (FCMs) are sources of food contamination and human chemical exposure. Some chemicals in these materials are known to cause adverse effects, but many are poorly characterized for their potential toxicological hazards making risk assessment a challenge. The aim of the project was to obtain knowledge on the potential hazards posed by chemicals present in FCMs through examining compounds with known usages or suspected of being used in these materials, namely bisphenol A (BPA), BPA analogues and fluorinated substances.

Furthermore, we developed a strategy to identify problematic compounds present in these materials. Specific focus was placed on in vitroendpoints assessing endocrine activity. BPA, five BPA analogues, and 19 fluorinated substances including fluorochemical containing technical mixtures (TMs) were investigated.

The in vitro assays included the androgen receptor (AR), estrogen receptor (ER), aryl hydrocarbon receptor, retinoic acid receptor, glucocorticoid receptor, p53, and nuclearfactor (erythroid-derived 2)-like 2 reporter gene assays, and the H295R steroidogenesis assay. The FCM strategy was a step-by-step procedure in which extracts from FCMs of paper and board were tested in vitro, active extracts were fractionated and tested in vitro, tentative identification was performed in active fractions, and tentatively identified compounds were tested in vitro and quantified in the extract.

BPA analogues generally led to similar estrogenic and antiandrogenic effects in vitro compared to BPA. However, the BPA analogue BPS caused less marked effects on most of these endpoints, but led to a more pronounced effects on progestagen levels compared to BPA. Likewise, the effects on corticoid levels in the H295R steroidogenesis assay differed between the six compounds.

These data suggest that the tested analogues overall have similar effects on the parameters investigated, though some differed. Therefore based on the presented data, the BPA analogues may not be suitable BPA alternatives. The fluorinated chemicals exhibited endocrine activities distinct from one another, but subgroups of fluorinated chemicals had similar profiles.

Polyfluoroalkyl phosphate ester surfactants (PAPs) generally decreased progestagen and androgen levels, fluorotelomer alcohols (FTOHs) generally increased ER activity, and long-chained perfluorinated alkyl carboxylic acids (PFCAs) generally increased 17β-estradiol levels. Two TMs caused estrogenicity in vitro, whereas none of the short-chained PFCAs caused effects.

It is recommended to conduct further studies on polyfluorinated chemicals as well as TMs to obtain more information on the implications of these differences in effect. The developed FCM strategy proved useful for identifying potential problematic compounds in FCMs of paper and board. All extracts from FCMs led to effects in at least one of the applied in vitro assays and we successfully identified five causative agents in two FCMs when applying the full strategy.

It is recommended to test more FCMs of paper and board with the strategy to obtain information on other potentially problematic compounds present in these materials. The presented data overall suggest that some compounds present in FCMs or suspected of being used can exert endocrine activities in vitro, though the implications of these findings with respect to effects in humans and exposure to humans remain largely unknown.

Nevertheless, it is of concern that so many of the materials and compounds led to effects and calls for further studies to be conducted. The data obtained in this PhD can be used as a prioritization tool for these purposes.