Phthalate esters (PEs) and organophosphate esters (OPEs) are common indoor pollutants frequently detected in environmental (dust, air), personal (hand wipes, diet) and human matrices (urine, serum etc.). In this thesis, mathematical models were used to establish links between intake and body burden for a comprehensive dataset based on a Norwegian study population. Also, the relative importance of different PE uptake pathways was assessed and discussed. Furthermore, the suitability of human nails as an alternative, non-invasive biomonitoring matrix for PEs was investigated. Additionally, information regarding alternative plasticizers to PEs was collected and presented extensively. Results showed that for PEs (paper II), daily intakes based on external exposure media agree with back-calculations using urinary metabolite concentrations, leading to the conclusion that human exposure for the general adult population is well understood and that the most important uptake routes were captured. Overall intake levels are comparable or lower than level presented in recent comprehensive studies and hazard quotients were well below 1 (low risk). As expected, diet was found to be the most important uptake route for all PEs. For lower molecular weight PEs, inhalation becomes a strong contributing pathway whereas for higher molecular weight PEs, dust ingestion was also important. Daily intake based on hand wipes was found to be much lower than the estimated total dermal intake based on air, dust and personal care products, questioning the relevance of hand wipes to represent total dermal exposure. Human nails were found to be unsuitable for replacing urine as a biomonitoring matrix for PEs as internal intake (from blood) cannot explain measured nail concentrations and uptake from air is too slow to reach observed concentrations within a realistic time frame (paper III). Hence, the kinetic links between intake and nail concentrations could not be established. Although exposure to traditional PEs is decreasing, use and body burden of some alternatives are increasing (paper I). Fortunately, most alternative plasticizers have favorable toxicological properties, resulting in low risk for humans. In contrast to PEs, OPEs still remain a group of poorly studied substances in terms of human exposure (paper IV). Due to lack of information regarding human metabolism, reliable links between intake and concentrations in serum and urine could not be established. Modelling results showed that concentrations in serum, and to some extent, urine, were underestimated for 2 compounds. It is likely that a combination of missing intake and suboptimal biomarkers were the cause for this under-prediction. Because of this, further studies regarding human metabolism should be performed for OPEs and potentially more specific biomarkers identified in the future. For PEs, there is a need for more comprehensive datasets to study exposure for high risk groups such as infants and children. Furthermore, dermal uptake remains poorly understood and the uptake of PEs into human nails should be studied in more detail to establish the kinetic links between exposure and body burden.

Phthalate esters (PEs) and alternative plasticizers used as additives in numerous consumer products are continuously released into the environment leading to subsequent human exposure. The ubiquitous presence and potential adverse health effects (e.g. endocrine disruption and reproductive toxicity) of some PEs are responsible for their bans or restrictions. This has led to increasing use of alternative plasticizers, especially cyclohexane-1,2-dicarboxylic acid diisononyl ester (DINCH). Human exposure data on alternative plasticizers are lacking and clear evidence for human exposure has previously only been found for di(2-ethylhexyl) terephthalate (DEHTP) and DINCH, with increasing trends in body burdens. In this thesis, a study population of 61 adults (age: 20–66; gender: 16 males and 45 females) living in the Oslo area (Norway) was studied for their exposure to plasticizers. Information on sociodemographic and lifestyle characteristics that potentially affect the concentrations of PE and DINCH metabolites in adults was collected by questionnaires. Using the human biomonitoring approach, we evaluated the internal exposure to PEs and DINCH by measuring concentrations of their metabolites in urine (where metabolism and excretion are well understood) and using these data to back-calculate daily intakes. Metabolite levels in finger nails were also determined. Since reference standards of human metabolites for other important alternative plasticizers apart from DINCH (e.g. DEHTP, di(2-propylheptyl) phthalate (DPHP), di(2-ethylhexyl) adipate (DEHA) and acetyl tributyl citrate (ATBC)) are not commercially available, we further investigated the urine and finger nail samples by Q Exactive Orbitrap LC-MS to identify specific metabolites, which can be used as appropriate biomarkers of human exposure. Many metabolites of alternative plasticizers that were present in in vitro extracts were further identified in vivo in urine and finger nail samples. Hence, we concluded that in vitro assays can reliably mimic the in vivo processes. Also, finger nails may be a useful non-invasive matrix for human biomonitoring of specific organic contaminants, but further validation is needed. Concentrations of PEs and DINCH were also measured in duplicate diet, air, dust and hand wipes. External exposure, estimated based on dietary intake, air inhalation, dust ingestion and dermal uptake, was higher or equal to the back-calculated internal intake. By comparing these, we were able to explain the relative importance of different exposure pathways for the Norwegian study population. Dietary intake was the predominant exposure route for all analyzed substances. Inhalation was important only for lower molecular weight PEs, while dust ingestion was important for higher molecular weight PEs and DINCH. Dermal uptake based on hand wipes was much lower than the total dermal uptake calculated via air, dust and personal care products, but still several research gaps remain for this exposure pathway. Based on calculated intakes, the exposure risk for the Norwegian participants to the PEs and DINCH did not exceed the established tolerable daily intake and reference doses, and the cumulative risk assessment for combined exposure to plasticizers with similar toxic endpoints indicated no health concerns for the selected population. Nevertheless, exposure to alternative plasticizers, such as DPHP and DINCH, is expected to increase in the future and continuous monitoring is required. Findings through uni- and multivariate analysis suggested that age, smoking, use of personal care products and many other everyday habits, such as washing hands or eating food from plastic packages are possible contributors to plasticizer exposure.