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Abstract

From the moment of conception until death, humans are exposed to chemicals at varying intensities and frequencies. While an individual’s level of resilience is commonly high enough to tolerate these kinds of stressors, specific exposures or genetic predispositions can lower it. Therefore, the assessment of chemical exposure, the development of analytical methods, the evaluation of the consequences for the population, and the assessment of individual susceptibilities are key aspects in exposome studies.
Within this dissertation, exposure to persistent organic pollutants (POPs), and non-persistent compounds, such as phthalates (PHs) and their alternatives, bisphenols (BPs), parabens (PBs), and triclosan (TCS) was assessed in two populations of 1) men and primiparous lactating women from Slovenia (first national human biomonitoring (HBM) project in Slovenia) and of 2) Slovenian men, women, and children (DEMOCOPHES). Potential exposure sources and differences in exposure were determined using questionnaire data. The results revealed that the Slovenian population is widely exposed to PHs and di(isononyl)cyclohexane-1,2-dicarboxylate, Hexamoll®DINCH (DINCH) and common BPs and PBs, whereas the levels of less-common BPs, PBs, and TCS were low. Likewise, exposure to POPs is low, especially if compared to populations from the Northern side of the Alps, whereas in Slovenia, POP levels were the highest in Bela krajina and Ljubljana. Associations with questionnaire data revealed that the most common sources of exposure for POPs, high molecular weight PHs, DINCH, and BPs were dietary, whereas exposure to PBs and low molecular weight PHs is mostly related to personal care products. We observed differences in exposure based on sociodemographic characteristics and the residential environment.
In the form of a review study, we summarized and evaluated analytical methods for the determination of contaminants of emerging concern (CECs) and concluded that the existing methods are suitable for application in HBM studies and do not require out-of-the-norm modifications in the laboratory.
To assess the possibility of harmful health effects resulting from exposure to PHs, DINCH, BPs, PBs, and TCS, we calculated the hazard quotient that is below the threshold of 1 for the evaluated population and contaminants. We suggest to repeat this assessment on other populations and to include a wider range of analytes.
As genetic predisposition can influence a person’s detoxification ability, we investigated for the first time the influence of single nucleotide polymorphisms (SNPs) in genes of cytochrome P450 enzymes (CYPs) and UDP-glucuronyl transferases (UGTs) that can influence the biotransformation of PHs and DINCH using HBM data. The results indicate that SNPs in genes of CYP2C9, CYP2C19, CYP2D6, UGT2B15 and UGT1A7 can influence the biotransformation of PHs and DINCH and are, therefore, suitable biomarkers of susceptibility.
From this dissertation we can conclude that the available analytical methods for determining CECs are appropriate in the implementation of HBM. The Slovenian population is exposed to selected chemicals through food, personal care products, and the living environment. Exposure levels generally do not exceed critical thresholds, but cumulative exposure to multiple chemicals at the same time and genetic susceptibility should be considered in the risk assessment. An important result of this work is also the identification of biomarkers of susceptibility to PH and DINCH exposure.