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Probing the relationship between external and internal human exposure of organophosphate flame retardants using pharmacokinetic modelling
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

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.

Keywords [en]
flame retardants, human exposure, pharmacokinetic modelling, metabolism
National Category
Environmental Sciences
Identifiers
URN: urn:nbn:se:su:diva-141807OAI: oai:DiVA.org:su-141807DiVA, id: diva2:1089096
Funder
EU, FP7, Seventh Framework Programme, 316665Available from: 2017-04-18 Created: 2017-04-18 Last updated: 2017-04-27Bibliographically approved
In thesis
1. Assessing human exposure to phthalates, alternative plasticizers and organophosphate esters
Open this publication in new window or tab >>Assessing human exposure to phthalates, alternative plasticizers and organophosphate esters
2017 (English)Doctoral thesis, comprehensive summary (Other academic) [Artistic work]
Abstract [en]

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.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science and Analytical Chemistry, Stockholm University, 2017. p. 59
Keywords
Human exposure, phthalates, organophosphates, plasticizers, flame retardants, modelling
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-141808 (URN)978-91-7649-698-5 (ISBN)978-91-7649-699-2 (ISBN)
Public defence
2017-06-01, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 13:00 (English)
Opponent
Supervisors
Funder
EU, FP7, Seventh Framework Programme, 316665
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 4: Manuscript.

Available from: 2017-05-09 Created: 2017-04-18 Last updated: 2017-05-10Bibliographically approved

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