Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Estimating uptake of phthalate ester metabolites into the human nail plate using pharmacokinetic modelling
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. IVL Swedish Environmental Research Institute, Sweden.
Show others and affiliations
Number of Authors: 62017 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 100, p. 148-155Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 100, p. 148-155
Keywords [en]
Human nail, Phthalates, Pharmacoldnetic modelling, partitioning
National Category
Earth and Related Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
URN: urn:nbn:se:su:diva-141220DOI: 10.1016/j.envint.2017.01.007ISI: 000394076900010PubMedID: 28089278OAI: oai:DiVA.org:su-141220DiVA, id: diva2:1089552
Available from: 2017-04-20 Created: 2017-04-20 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

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Bui, Thuy T.Cousins, Ian T.
By organisation
Department of Environmental Science and Analytical Chemistry
In the same journal
Environment International
Earth and Related Environmental Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 60 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf