| 1. |
- Bui, Thuy T., et al.
(författare)
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Estimating uptake of phthalate ester metabolites into the human nail plate using pharmacokinetic modelling
- 2017
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 100, s. 148-155
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of knowledge regarding uptake of phthalate esters (PEs) and other chemicals into the human nail plate and thus, clarity concerning the suitability of human nails as a valid alternative matrix for monitoring longterm exposure. In particular, the relative importance of internal uptake of phthalate metabolites (from e.g. blood) compared to external uptake pathways is unknown. This study provides first insights into the partitioning of phthalate-metabolites between blood and nail using pharmacokinetic (PK) modelling and biomonitoring data from a Norwegian cohort. A previously published PK model (Lorber PK model) was used in combination with measured urine data to predict serum concentrations of DEHP and DnBP/DiBP metabolites at steady state. Then, partitioning between blood and nail was assessed assuming equilibrium conditions and treating the nail plate as a tissue, assuming a fixed lipid and water content. Although calculated as a worst-case scenario at equilibrium, the predicted nail concentrations of metabolites were lower than the biomonitoring data by factors of 44 to 1300 depending on the metabolite. It is therefore concluded that internal uptake of phthalate metabolites from blood into nail is a negligible pathway and does not explain the observed nail concentrations. Ingtead, external uptake pathways are more likely to dominate, possibly through deposition of phthalates onto the skin/nail and subsequent metabolism. Modelling gaseous diffusive uptake of PEs from air to nail revealed that this pathway is unlikely to be important. Experimental quantification of internal and external uptake pathways of phthalates and their metabolites into the human nail plate is needed to verify these modelling results. However, based on this model, human nails are not a good indicator of internal human exposure for the phthalate esters studied.
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| 2. |
- Bui, Thuy T., et al.
(författare)
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Human exposure, hazard and risk of alternative plasticizers to phthalate esters
- 2016
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 541, s. 451-467
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Tidskriftsartikel (refereegranskat)abstract
- Alternative plasticizers to phthalate esters have been used for over a decade, but data regarding emissions, human exposure and health effects are limited. Here we review 20 alternative plasticizers in current use and their human exposure, hazard and risk. Physicochemical properties are collated for these diverse alternatives and log K-OW values range over 15 orders of magnitude and log K-AW and log K-OA values over about 9 orders of magnitude. Most substances are hydrophobic with low volatility and are produced in high volumes for use in multiple applications. There is an increasing trend in the total use of alternative plasticizers in Sweden compared to common phthalate esters in the last 10 years, especially for DINCH. Evaluative indoor fate modeling reveals that most alternatives are distributed to vertical surfaces (e.g. walls or ceilings). Only TXIB and GTA are predicted to be predominantly distributed to indoor air. Human exposure data are lacking and clear evidence for human exposure only exists for DEHT and DINCH, which show increasing trends in body burdens. Human intake rates are collected and compared with limit values with resulting risk ratios below 1 except for infant's exposure to ESBO. PBT properties of the alternatives indicate mostly no reasons for concern, except that TEHPA is estimated to be persistent and TCP toxic. A caveat is that non-standard toxicological endpoint results are not available and, similar to phthalate esters, the alternatives are likely pseudo-persistent. Keydata gaps for more comprehensive risk assessment are identified and include: analytical methods to measure metabolites in biological fluids and tissues, toxicological information regarding non-standard endpoints such as endocrine disruption and a further refined exposure assessment in order to consider high risk groups such as infants, toddlers and children.
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| 3. |
- Bui, Thuy T., et al.
(författare)
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Probing the relationship between external and internal human exposure of organophosphate flame retardants using pharmacokinetic modelling
- 2017
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 230, s. 550-560
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Tidskriftsartikel (refereegranskat)abstract
- Human external exposure (i.e. intake) of organophosphate flame retardants (PFRs) has recently been quantified, but no link has yet been established between external and internal exposure. In this study, we used a pharmacokinetic (PK) model to probe the relationship between external and internal exposure data for three PFRs (EHDPHP, TNBP and TPHP) available for a Norwegian cohort of 61 individuals from 61 different households. Using current literature on metabolism of PFRs,, we predicted the metabolite serum/urine concentrations and compared it to measured data from the study population. Unavailable parameters were estimated using a model fitting approach (least squares method) after assigning reasonable constraints on the ranges of fitted parameters. Results showed an acceptable comparison between PK model estimates and measurements (<10-fold deviation) for EHDPHP. However, a deviation of 10-1000 was observed between PM model estimates and measurements for TNBP and TPHP. Sensitivity and uncertainty analysis on the PK model revealed that EHDPHP results showed higher uncertainty than TNBP or TPHP. However, there are indications that (1) current biomarkers of exposure (i.e. assumed metabolites) for TNBP and TPHP chemicals might not be specific and ultimately affecting the outcome of the modelling and (2) some exposure pathways might be missing. Further research, such as in vivo laboratory metabolism experiments of PFRs including identification of better biomarkers will reduce uncertainties in human exposure assessment.
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| 4. |
- Bui, Tuong Thuy, et al.
(författare)
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Probing the relationship between external and internal human exposure of organophosphate flame retardants using pharmacokinetic modelling
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Human external exposure (i.e. intake) of organophosphate flame retardants (PFRs) has recently been quantified, but no link has yet been established between external and internal exposure. In this study, we used a pharmacokinetic (PK) model to probe the relationship between external and internal exposure data for three PFRs (EHDPHP, TNBP and TPHP) available for a Norwegian cohort of 61 individuals from 61 different households. Using current literature on metabolism of PFRs, we predicted the human body burden and compared it to the measured serum and urine data for the PFRs metabolites. Unavailable parameters were estimated using a model fitting approach (least squares method) after assigning reasonable constraints on the ranges of fitted parameters. Results showed an acceptable comparison between PK model estimates and measurements (< 10-fold deviation) for EHDPHP. However, a deviation of 10-1000 was observed between PK model estimates and measurements for TNBP and TPHP. Sensitivity and uncertainty analysis on the PK model revealed that EHDPHP results showed higher uncertainty than TNBP or TPHP. However, there are indications that (1) current biomarkers of exposure (i.e. assumed metabolites) for TNBP and TPHP chemicals might not be specific and ultimately affecting the outcome of the modeling, (2) some exposure pathways might be missing. Further research, such as in vivo laboratory metabolism experiments of PFRs including identification of better biomarkers will reduce uncertainties in human exposure assessment.
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| 5. |
- Giovanoulis, Georgios, et al.
(författare)
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Multi-pathway human exposure assessment of phthalate esters and DINCH
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 112, s. 115-126
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Tidskriftsartikel (refereegranskat)abstract
- Phthalate esters are substances mainly used as plasticizers in various applications. Some have been restricted and phased out due to their adverse health effects and ubiquitous presence, leading to the introduction of alternative plasticizers, such as DINCH. Using a comprehensive dataset from a Norwegian study population, human exposure to DMP, DEP, DnBP, DiBP, BBzP, DEHP, DINP, DIDP, DPHP and DINCH was assessed by measuring their presence in external exposure media, allowing an estimation of the total intake, as well as the relative importance of different uptake pathways. Intake via different uptake routes, in particular inhalation, dermal absorption, and oral uptake was estimated and total intake based on all uptake pathways was compared to the calculated intake from biomonitoring data. Hand wipe results were used to determine dermal uptake and compared to other exposure sources such as air, dust and personal care products. Results showed that the calculated total intakes were similar, but slightly higher than those based on biomonitoring methods by 1.1 to 3 times (median), indicating a good understanding of important uptake pathways. The relative importance of different uptake pathways was comparable to other studies, where inhalation was important for lower molecular weight phthalates, and negligible for the higher molecular weight phthalates and DINCH. Dietary intake was the predominant exposure route for all analyzed substances. Dermal uptake based on hand wipes was much lower (median up to 2000 times) than the total dermal uptake via air, dust and personal care products. Still, dermal uptake is not a well-studied exposure pathway and several research gaps (e.g. absorption fractions) remain. Based on calculated intakes, the exposure for the Norwegian participants to the phthalates and DINCH was lower than health based limit values. Nevertheless, exposure to alternative plasticizers, such as DPHP and DINCH, is expected to increase in the future and continuous monitoring is required.
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| 6. |
- Giovanoulis, Georgios, et al.
(författare)
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Multi-pathway human exposure assessment of phthalate esters and DINCH
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Phthalate esters are substances mainly used as plasticizers in various applications. Some have been restricted and phased out due to their adverse health effects and ubiquitous presence, leading to the introduction of alternative plasticizers, such as DINCH. Using a comprehensive dataset from a Norwegian study population, human exposure to DMP, DEP, DnBP, DiBP, BBzP, DEHP, DINP, DIDP, DPHP and DINCH was assessed by measuring their presence in external exposure media, allowing an estimation of the total intake, as well as the relative importance of different uptake pathways. Intake via different uptake routes, in particular inhalation, dermal absorption, and oral uptake was estimated and total intake based on all uptake pathways was compared to the back-calculated intake from biomonitoring data. Hand wipe results were used to determine dermal uptake and compared to other exposure sources such as air, dust and personal care products. Results showed that the calculated total intakes were similar, but slightly higher than those based on biomonitoring methods by 1.1 to 2.8 times (median), indicating a good understanding of important uptake pathways. The relative importance of different uptake pathways was comparable to other studies, where inhalation was important for lower molecular weight phthalates, and negligible for the higher molecular weight phthalates and DINCH. Dietary intake was the predominant exposure route for all analyzed substances. The dermal uptake assessed by hand wipes was much lower (median up to 2000 times) than the sum of dermal uptake via air, dust and personal care products and unlikely represents an integrative dermal exposure. Dermal uptake is not a well-studied exposure pathway and several research gaps (e.g. absorption fractions) remain. Based on calculated intakes, the exposure risk for the Norwegian participants to the phthalates and DINCH was lower than health based limit values. Nevertheless, exposure to alternative plasticizers, such as DPHP and DINCH, is expected to increase in the future and continuous monitoring is required.
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| 7. |
- Liagkouridis, Ioannis, et al.
(författare)
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Emissions and fate of brominated flame retardants in the indoor environment : A critical review of modelling approaches
- 2014
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 491, s. 87-99
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Forskningsöversikt (refereegranskat)abstract
- This review explores the existing understanding and the available approaches to estimating the emissions and fate of semi-volatile organic compounds (SVOCs) and in particular focuses on the brominated flame retardants (BFRs). Volatilisation, an important emission mechanism for the more volatile compounds can be well described using current emission models. More research is needed, however, to better characterise alternative release mechanisms such as direct material-particle partitioning and material abrasion. These two particle-mediated emissions are likely to result in an increased chemical release from the source than can be accounted for by volatilisation, especially for low volatile compounds, and emission models need to be updated in order to account for these. Air-surface partitioning is an important fate process for SVOCs such as BFRs however it is still not well characterised indoors. In addition, the assumption of an instantaneous air-particle equilibrium adopted by current indoor fate models might not be valid for high-molecular weight, strongly sorbing compounds. A better description of indoor particle dynamics is required to assess the effect of particle-associated transport as this will control the fate of low volatile BFRs. We suggest further research steps that will improve modelling Precision and increase our understanding of the factors that govern the indoor fate of a wide range of SVOCs. It is also considered that the appropriateness of the selected model for a given study relies on the individual characteristics of the study environment and scope of the study.
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| 8. |
- Liagkouridis, Ioannis, et al.
(författare)
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Physical-chemical properties and evaluative fate modelling of 'emerging' and 'novel' brominated and organophosphorus flame retardants in the indoor and outdoor environment
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 524, s. 416-426
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Tidskriftsartikel (refereegranskat)abstract
- Several groups of flame retardants (FRs) have entered the market in recent years as replacements for polybrominated diphenyl ethers (PBDEs), but little is known about their physical-chemical properties or their environmental transport and fate. Here we make best estimates of the physical-chemical properties and undertake evaluative modelling assessments (indoors and outdoors) for 35 so-called 'novel' and 'emerging' brominated flame retardants (BFRs) and 22 organophosphorus flame retardants (OPFRs). A QSPR (Quantitative Structure-Property Relationship) based technique is used to reduce uncertainty in physical-chemical properties and to aid property selection for modelling, but it is evident that more, high quality property data are required for improving future assessments. Evaluative modelling results show that many of the alternative FRs, mainly alternative BFRs and some of the halogenated OPFRs, behave similarly to the PBDEs both indoors and outdoors. These alternative FRs exhibit high overall persistence (Pov), long-range transport potential (LRTP) and POP-like behaviour and on that basis cannot be regarded as suitable replacements to PBDEs. A group of low molecular weight alternative BFRs and non-halogenated OPFRs show a potentially better environmental performance based on Pov and LRTP metrics. Results must be interpreted with caution though since there are significant uncertainties and limited data to allow for thorough model evaluation. Additional environmental parameters such as toxicity and bioaccumulative potential as well as functionality issues should be considered in an industrial substitution strategy.
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| 9. |
- Liagkouridis, Ioannis, et al.
(författare)
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Relationships between estimated flame retardant emissions and levels in indoor air and house dust
- 2017
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Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 27:3, s. 650-657
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Tidskriftsartikel (refereegranskat)abstract
- A significant number of consumer goods and building materials can act as emission sources of flame retardants (FRs) in the indoor environment. We investigate the relationship between the emission source strength and the levels of 19 brominated flame retardants (BFRs) and seven organophosphate flame retardants (OPFRs) in air and dust collected in 38 indoor microenvironments in Norway. We use modeling methods to back-calculate emission rates from indoor air and dust measurements and identify possible indications of an emission-to-dust pathway. Experimentally based emission estimates provide a satisfactory indication of the relative emission strength of indoor sources. Modeling results indicate an up to two orders of magnitude enhanced emission strength for OPFRs (median emission rates of 0.083 and 0.41gh(-1) for air-based and dust-based estimates) compared to BFRs (0.52 and 0.37ngh(-1) median emission rates). A consistent emission-to-dust signal, defined as higher dust-based than air-based emission estimates, was identified for four of the seven OPFRs, but only for one of the 19 BFRs. It is concluded, however, that uncertainty in model input parameters could potentially lead to the false identification of an emission-to-dust signal.
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| 10. |
- Anderson, J. K., et al.
(författare)
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Grouping of PFAS for human health risk assessment : Findings from an independent panel of experts
- 2022
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Ingår i: Regulatory toxicology and pharmacology. - : Elsevier. - 0273-2300 .- 1096-0295. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information.
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