Determining the major human exposure pathways is a prerequisite for the development of effective management strategies for environmental pollutants such as chlorinated paraffins (CPs). As a first step, the internal and external exposure to CPs were quantified for a well-defined human cohort. CPs in participants’ plasma and diet samples were analyzed in the present study, and previous results on paired air, dust, and hand wipe samples were used for the total exposure assessment. Both one compartment pharmacokinetic modeling and forensic fingerprinting indicate that dietary intake contributed the most to body burden of CPs in this cohort, contributing a median of 60–88% of the total daily intakes. The contribution from dust ingestion and dermal exposure was greater for the intake of long-chain CPs (LCCPs) than short-chain CPs (SCCPs), while the contribution from inhalation was greater for the intake of SCCPs than medium-chain CPs (MCCPs) and LCCPs. Significantly higher concentrations of SCCPs and MCCPs were observed in diets containing butter and eggs, respectively (p < 0.05). Additionally, other exposure sources were correlated to plasma levels of CPs, including residence construction parameters such as the construction year (p < 0.05). This human exposure to CPs is not a local case. From a global perspective, there are major knowledge gaps in biomonitoring and exposure data for CPs from regions other than China and European countries.

Very-short- (vSCCPs, C6-9), short- (SCCPs, C10-13), medium-(MCCPs, C14-17), and long-chain chlorinated paraffins (LCCPs, C->17) were analyzed in indoor air and dust collected from the living rooms and personal 24 h air of 61 adults from a Norwegian cohort. Relatively volatile CPs, i.e., vSCCPs and SCCPs, showed a greater tendency to partition from settled indoor dust to paired stationary indoor air from the same living rooms than MCCPs and LCCPs, with median logarithmic dust-air partition ratios of 1.3, 2.9, 4.1, and 5.4, respectively. Using the stationary indoor air and settled indoor dust concentrations, the combined median daily exposures to vSCCPs, SCCPs, MCCPs, and LCCPs were estimated to be 0.074, 2.7, 0.93, and 0.095 ng/kg bw/d, respectively. Inhalation was the predominant exposure pathway for vSCCPs (median 99%) and SCCPs (59%), while dust ingestion was the predominant exposure pathway for MCCPs (75%) and LCCPs (95%). The estimated inhalation exposure to total CPs was similar to 5 times higher when the personal 24 h air results were used rather than the corresponding stationary indoor air results in 13 paired samples, indicating that exposure situations other than living rooms contributed significantly to the overall personal exposure. The 95th percentile exposure for CPs did not exceed the reference dose.

Up to 18000 ng of total chlorinated paraffins (CPs) was found in hand wipes of individual adult participants in a Norwegian cohort study (n = 60), with a geometric mean (SD) value of 870 (2700) ng. The CPs covered a wide range of alkane chain lengths from C-7 to C-48 with variable chlorine substitution. Complex mixtures of very-short-chain (vSCCPs, C-<10), short-chain (SCCPs, C10-13), medium-chain (MCCPs, C14-17), and long-chain (LCCPs, C->17) CPs were found, contributing on average 0.3%, 20%, 58%, and 22%, respectively, of the total CPs. Significant positive correlations were found between CP levels and factors related to the indoor environment and product use, including living in a house/apartment built before the ban of SCCPs, having a sofa, the number of TVs in the home, and owning a car, which mirrors CP usage as flame retardants and/or plasticizers in consumer products. Compared to previous studies of other organic contaminants in hand wipe samples from the same cohort, CPs were the most abundant flame retardants. This is the first report of CPs in hand wipes, and dermal exposure based on these data suggested that hand contact could be an important human exposure pathway for LCCPs.

Sixty-one serum samples from a Norwegian cohort were analyzed for 43 emerging and legacy halogenated flame retardants (HFRs). BDE-47, -153, -197 and -209 were detected in > 56% of the samples with median concentrations of 0.23, 1.0, 0.64 and 1.5 ng/g lipid, respectively. BDE-49, -85, -99, -100, -154, -206, -207, 208 as well as HBB, syn- and anti-DDC-CO, OBTMPI, DBDPE, alpha-HBCDD and TBBPA were also detected in some serum samples (detection frequencies of 2-36%). Other tri-octaBDEs, TBP-AE, alpha- and beta-DBE-DBCH, BATE, pTBX, alpha beta-TBCO, PBBz, TBCT, PBT, PBEB, DPTE, EH-TBB, BTBPE, BEH-TEBP, HCDBCO, beta- and gamma-HBCDD were below the limits of detection (mLOD). Concentrations of individual BDE congeners detected in this study were within the range from previous European studies. Positive correlations were seen between concentrations of BDE-47 in dust and BDE-153 in serum, between BDE-153 in dust and BDE-153 in serum, and between BDE-153 masses in handwipes and BDE-47 concentrations in serum (Spearman's rank, 0.29 < r < 0.43). Associations between the number of phones/mobiles, numbers of electronic equipment per person in the home and the consumption of specific food categories (such as soups/spices/sauces and alcoholic beverages) with BDE-47 and -153 serum levels were confirmed by multivariate linear regression analyses. The measured median serum level of BDE-47 was slightly over-predicted by a factor of 5.5 whereas other BDE congeners were under-predicted by factors of 13-6000 when compared to serum concentrations predicted from external exposure media (inhalation, dermal uptake, dietary intake from duplicate diet and dust ingestion) using a simple one compartment pharmacokinetic (PK) model. BDE-153 was not detected and BDE-197 not analyzed in food so no dietary intake assessments for these could be made, which may partially explain the discrepancies between their measured and predicted serum concentrations. Overall, our results suggest that exposure via diet is the most important exposure pathway for BDE-47 and -209, with diet being responsible for more than 96% of the total daily intake of these two BDEs in the Norwegian cohort.

There are few studies estimating dermal exposure to halogenated flame retardants in adults. To fill this gap, sixty-one hand wipe samples were collected from a Norwegian adult cohort using gauze pads immersed in isopropanol. BDE-47, BDE-209, bis(2‑ethyl‑hexyl)‑3,4,5,6‑tetrabromophthalate (BEH-TEBP) and decabromodiphenylethane (DBDPE) were the most frequently detected chemicals. The highest median mass in hand wipes was that of sumEHFR (570 ng), followed by sumHBCDD (180 ng) and sumPBDE (2.9 ng). The high EHFR level was mainly driven by tetrabromobisphenol A (TBBPA) which accounted for 77% of the total mass. Positive and significant correlations were observed between FR levels in hand wipes and settled dust (0.26 < r < 0.56, p < 0.05), as well as between FR levels in hand wipes and the number of electronic consumer products at home (0.27 < r < 0.40, p < 0.05). Significant bivariate associations with number of laptops/tablets and phones/mobiles were further confirmed by multivariate linear regression analyses. Dermal exposure was estimated using the levels measured in handwipes. The estimated median dermal exposure was 2600, 840 and 6.2 pg/kg bw/d for sumEHFR, sumHBCDD and sumPBDE, respectively. Further, we compared these results with the dermal exposure as estimated indirectly by utilizing previously reported FR levels in settled dust collected from the residences of the same studied cohort. With the indirect approach, higher dermal exposures to sumPBDE but lower exposures to sumEHFR and sumHBCDD were observed compared to the direct dermal exposure estimated via hand wipes. Comparable exposure estimates between hand wipes and the indirect method were obtained for α‑, β‑tetrabromoethylcyclohexane (DBE-DBCH), DBDPE, BDE-28, -35, -49, -99, -153, 154, and -183. For other individual HFRs, the exposure estimates obtained from the two approaches were significantly different (Mann-Whitney U test, p < 0.05). Both methods gave similar dermal exposure estimates for many individual FRs. However, it is important to be aware of the value and limitations of each method when using them to estimate human exposure.

Flame retardants (FRs) are chemicals added to a broad range of consumer products such as textiles, electrical and electronic equipment, furniture and building material to meet flammability requirements. Most of these chemicals are additives that can continuously leach out from the applied products during usage. FRs are studied because of their abundance in indoor environments and concerns about their impact on human health. The restrictions on many brominated FRs have resulted in a need for their replacement with a variety of emerging halogenated FRs (EHFRs). Humans are exposed to these chemicals mainly through dust and diet ingestion, but there is still insufficient data about the relative importance of other exposure pathways. In this thesis, a Norwegian cohort of 61 adults (age 20-66, 16 males and 45 females) was studied for their exposure to legacy and emerging HFRs. Duplicate diet, stationary air, personal air, settled dust, hand wipe and serum samples were collected from the participants and analyzed for polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs) and EHFRs. External exposures via dietary intake, air inhalation, dust ingestion and dermal exposure (in pg/kg body weight/day) were estimated from the measured concentrations. The intake values were then compared to elucidate which of these exposure pathways were most important for the Norwegian cohorts’ exposure to specific HFRs. Dietary intake was the predominant exposure route for most of the PBDE congeners and EHFRs, whereas dust ingestion contributed significantly to the exposure of some less volatile HFRs. Inhalation exposure was negligible for most of the target HFRs except for those with higher volatility, such as tetrabromoethylcyclohexane (DBE-DBCH), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 1,2,3,4,5-pentabromobenzene (PBBz). Dermal exposure seems to be a significant exposure pathway for HBCDDs and tetrabromobisphenol A (TBBPA) but the relevance of hand wipes to represent total dermal exposure remains uncertain. Overall, the median and 95^th percentile total intakes for all target HFRs did not exceed the regulatory reference doses (RfD). Estimated serum concentrations were calculated from total intakes from all exposure pathways using a one compartment pharmacokinetic model and these were compared to measured concentrations. The estimated median serum BDE-47 and BDE-153 concentrations were slightly over-estimated by a factor of 5.5 and 4.3, respectively whereas BDE-197 and -209 were under-estimated by 1 to 2 orders of magnitude compared to the measured concentrations. Statistical analysis suggested that age, number of electronic equipment at home, certain dietary habits, hand washing and house cleaning frequency were possible contributors to HFR exposure.

Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), emerging halogenated flame retardants (EHFRs) and organophosphate flame retardants (PFRs) were detected in 24 h duplicate diet samples from a Norwegian cohort (n = 61), with concentrations ranging from <method limit of quantification (MLQ)-0.64 ng/g ww, <MLQ-0.70 ng/g ww, <MLQ-0.93 ng/g ww, <MLQ-0.14 ng/g ww, and <MLQ-150 ng/g ww, respectively. All studied contaminants were detected in the duplicate diet samples with detection frequencies (DF) ranging from 1.6 to 98%. The major contaminants were CB153 (median 0.042 ng/g ww), alpha-HCH (median 0.22 ng/g ww), BDE209 (median 0.45 ng/g ww), ethyl hexyl diphenyl phosphate (EHDPHP) (median 3.0 ng/g ww) and bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (BEH-TEBP) (< MLQ-0.14 ng/g ww). Human dietary exposure assessment was conducted for each participant based on individual body weight and contaminant concentrations in their collected duplicate diet samples. The estimated median (95th percentile) dietary exposures for Sigma PFR, Sigma PCB, Sigma OCP, Sigma PBDE, and Sigma EHFR were 87 (340), 5.8 (27),11 (31), 1.3 (14), and <0.01 (3.4) ng/kg bw/day, respectively. The median and 95th percentile dietary exposures of most of the target analytes did not exceed the reference dose (RID), except for PCBs where 16% of the participants exceeded the RID. However, a relatively short period of such high intake is not expected to result in any adverse health effects. Participants of this cohort were exposed to higher levels of EHDPHP than any other FRs. Fish was the major dietary route for PCB, OCP and PBDE exposure, while meat was the main dietary exposure route for PFRs.

In this study, we estimated human exposure to polybrominated diphenyl ethers (PBDEs), hexabromocyclo-dodecanes (HBCDDs), and several emerging flame retardants (EFRs) via inhalation and dust ingestion. Sixty indoor stationary air samples, 13 personal air samples, and 60 settled dust samples were collected from a Norwegian cohort during winter 2013. PBDEs showed the highest median concentration in dust (1200 ng/g), followed by EFRs (730 ng/g) and HBCDDs (190 ng/g). The PBDE concentrations in dust were mainly driven by BDE-209 and those of EFRs by bis(2-ethylhexyl) tetrabromophthalate. EFRs predominated in stationary air samples, with 2-ethylhexyl 2,3,4,5-tetrabromo-benzoate and 4-(1,2-dibromoethyl)-1,2-dibromocyclohexane having the highest median concentrations (150 and 25 pg/m(3) (sum of alpha- and beta-isomers), respectively). Different profiles and concentrations were observed in personal air samples compared to the corresponding stationary air samples. In relation to inhalation exposure, dust ingestion appears to be the major exposure pathway to FRs (median total exposure 230 pg/kg bw/d, accounting for more than 65% of the total exposure) for the Norwegian cohort. The calculated exposure due to air inhalation was substantially lower when the stationary air concentrations were used rather than personal air concentrations (43 pg/kg bw/d versus 130 pg/kg bw/d). This suggests that other exposure situations (such as outdoors or in offices) contributed significantly to the overall personal exposure, which cannot be included by using only a stationary air sampling technique. The median and 95th percentile exposures for all target FRs did not exceed the reference dose.