The exposure of people to chemicals has been of increasing interest over the past decades covering a large number of chemicals including synthetic industrial chemicals and production by-products, such as phthalates, DINCH, parabens, bisphenols, triclosan, and persistent organic pollutants (POPs).Results from the DEMOCOPHES study as well as the first national HBM study (HBM I) suggest that Slovenian women, children, men, and lactating women are exposed to numerous contaminants simultaneously. We found associations between phthalate metabolite concentrations and plastic as well as personal care products¹, whereas exposure to POPs seems to be associated with the residential environments (old building materials, local contamination events) and the consumption of animal products². Additionally, we evaluated the risk resulting from exposure to phthalates, parabens, bisphenols, and triclosan using the hazard quotient³. The resulting values for men and lactating women are 0.76 and 0.74, respectively, suggesting no risk at the point. However, this approach neglects individual susceptibilities based on genetic predispositions. We investigated the influence of selected cytochrome P450 enzymes on the biotransformation of di-(2-ethylhexyl) phthalate DEHP⁴ and identified three single nucleotide polymorphisms (SNPs) in CYP2C9 (rs1799853, CYP2C9*2; rs1057910, CYP2C9*3) and CYP2C19 (rs12248560, CYP2C19*17) that influence the biotransformation. The results suggest that carriers of CYP2C9*2 and *3 have significantly reduced excretion of secondary metabolites (men only) and lower ratios among metabolites. Carriers of both variant alleles had the most pronounced negative effect on DEHP biotransformation. Carriers of CYP2C19*17 had significantly higher excretion of secondary metabolites, however no effect on the was observed on the ratios. We therefore propose the named SNPs as biomarkers of susceptibility or resilience towards DEHP. Currently, we are developing an offline sample preparation method for the analysis of phthalate and DINCH metabolites using liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for the application in HBM studies. In this method, we carefully selected - among others - metabolites of high molecular weight (> 7 c atoms) compounds to evaluate the influence of the proposed biomarkers of susceptibility on other compounds structurally similar to DEHP.