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. 2018 Nov 9;15(11):2514.
doi: 10.3390/ijerph15112514.

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

Annette M Krais  1 , Christina Andersen  2 , Axel C Eriksson  3 , Eskil Johnsson  4 , Jörn Nielsen  5 , Joakim Pagels  6 , Anders Gudmundsson  7 , Christian H Lindh  8 , Aneta Wierzbicka  9
Affiliations

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

Annette M Krais et al. Int J Environ Res Public Health. .

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.

Keywords: human biomonitoring; human exposure studies; indoor air pollution; indoor environment; phthalate esters.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Analysed metabolites of diethyl phthalate (DEP) and bis(2-ethylhexyl) phthalate (DEHP) in this study, adapted from Koch et al. [23].
Figure 2
Figure 2
Excretion kinetics of D4-MEP. Excretion of the urinary metabolite D4-MEP from 16 participants over mid-time (mid time point of collection interval) after combined inhalation and dermal exposure to D4-DEP (A) and dermal only exposure to D4-DEP (B). The y-axis is presented in a logarithmic scale, and time points are given in mid-time (mid time point of collection interval).
Figure 3
Figure 3
Excretion kinetics of D4-DEHP metabolites. Urinary metabolites from 16 participants over mid-time (mid time point of collection interval) after combined inhalation and dermal exposure of D4-DEHP: sum of all five analysed metabolites (A), and D4-MEHP (B), D4-5OH-MEHP (C), D4-5oxo-MEHP (D), D4-5cx-MEPP (E), D4-2cx-MMHP (F), respectively. The y-axis is presented on a logarithmic scale, and time points are given in mid-time (mid time point of collection interval).
Figure 4
Figure 4
Total excreted dose after combined inhalation and dermal exposure to D4-DEP (A) and dermal exposure to D4-DEP only (B) as well as inhalation and dermal exposure of D4-DEHP (C). Cumulative excreted metabolite levels (in nmol) were normalised to air concentration of phthalate esters (in nmol/m3 air volume). The y-axis is presented on a logarithmic scale, and time points are given in mid-time (mid time point of collection interval).
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