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Cited by 43Effects and risks of endocrine disrupting chemicalsPesticide Exposure and ToxicityToxic Organic Pollutants Impact

Excretion of Urinary Metabolites of the Phthalate Esters DEP and DEHP in 16 Volunteers after Inhalation and Dermal Exposure

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Krais, Annette M., Andersen, Christina, Eriksson, Axel C., Johnsson, Eskil, Nielsen, Jörn, Pagels, Joakim, Gudmundsson, Anders, Lindh, Christian H. +1 more·2018·International Journal of Environmental Research and Public Health
DOI 10.3390/ijerph15112514PMC PMC6266104
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Abstract

Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100–300 µg/m3 of deuterium-labelled diethyl phthalate (D4-DEP) and bis(2-ethylhexyl) phthalate (D4-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D4-DEP and D4-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D4-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m3 (nmol of urinary metabolites per phthalates air concentration in (nmol/m3)). After dermal exposure to D4-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m3. After combined inhalation and dermal exposure to D4-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m3 between participants. No dermal uptake of particle phase D4-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D4-DEP was three times higher than after combined exposure to D4-DEHP; and nine times higher than after dermal exposure of D4-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.

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Crossref · 10.3390/ijerph15112514

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  • Urinary elimination of MEP was fast, with a mean apparent urinary elimination half-life of 8 hours, which was longer than the previously reported 2.7 (0.7-11) hours.

    “Urinary elimination of MEP was fast with a mean apparent urinary elimination half-life of 8 hours (Fig. 3), which was longer than previ­ ously reported in another study (2.7 (0.7 -11) hours (Krais et al., 2018)).”

    From Human skin absorption of three phthalates (2024) · cites this paper as Krais et al., 2018

    Section 3.1 reports a mean D4-MEP urinary excretion half-life of 2.7 hours after dermal exposure, supporting the cited comparison value. The cited paper’s text does not report the accompanying 0.7–11-hour range. The 8-hour estimate belongs to the citing study, not the claim attributed to Krais et al. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Urinary metabolites were almost equally distributed at all times post-exposure, similar to what was observed after inhalation.

    “Urinary metabolites were almost equally distributed at all times post-exposure, similar to what was observed after inhalation (Krais et al., 2018).”

    From Human skin absorption of three phthalates (2024) · cites this paper as Krais et al., 2018

    Section 3.2 reports that some oxidised DEHP metabolites reached urinary levels comparable to the monoester after combined inhalation and dermal exposure. It does not establish that metabolites were almost equally distributed at all post-exposure times: their peak times differed, and one metabolite had a much lower peak level. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Phthalate metabolite distributions vary depending on the route of entry.

    “Phthalate metabo­ lite distributions vary depending on the route of entry (Krais et al., 2018; Liss et al., 1985; Peck and Albro, 1982).”

    From Human skin absorption of three phthalates (2024) · cites this paper as Krais et al., 2018

    Section 3.1 reports different urinary metabolite levels and peak times after dermal versus combined inhalation and dermal exposure to DEP. Section 3.2 reports that DEHP metabolites were below detection after dermal exposure but detectable after combined exposure. These findings support route-dependent excretion, but the paper does not establish that the relative distribution among different metabolites changes with route. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Krais, A. M., Andersen, C., Eriksson, A. C., Johnsson, E., Nielsen, J., Pagels, J., Gudmundsson, A., Lindh, C. H., & Wierzbicka, A.
Affiliations
  • Lund University (SE)
  • Medicon Village (SE)
  • Division of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University, SE-22363 Lund, Sweden
Corresponding author
Krais, Annette M.
ORCID
Venue
International Journal of Environmental Research and Public Health
Publisher
MDPI AG
Published
2018-11-09
Volume
15
Issue
11
Pages
2514
ISSN
1660-4601 (ISSN-L)
DOI
10.3390/ijerph15112514
PMC
PMC6266104
OpenAlex
W2899589527
Cited by
43
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 1 · 2019: 7
FWCI
1.85
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Environmental Research and Public Health (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
Svenska Forskningsrådet Formas (216-2013-1478, 216-2013-1966)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Keywords
phthalates, diethyl phthalate, DEHP, urinary metabolites, inhalation exposure, dermal exposure, endocrine disruptors, human exposure assessment, interindividual variability
MeSH terms
Adult, Diethylhexyl Phthalate, Environmental Exposure, Female, Humans, Male, Middle Aged, Phthalic Acids, Sweden, Volunteers, Inhalation Exposure, Endocrine Disruptors, Young Adult

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