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Human skin absorption of three phthalates.

Nancy B Hopf¹, Hélène P De Luca¹, Myriam Borgatta¹

¹Center for Primary Care and Public Health (Unisanté), University of Lausanne, Route de la Corniche 2, Epalinges, Lausanne 1066, Switzerland; Swiss Center for Applied Human Toxicology (SCAHT), Basel.

Toxicology Letters

|June 16, 2024

Summary

Phthalates like DEP and DBP are absorbed through human skin, with emulsions increasing uptake. In vitro skin permeation studies accurately predict in vivo phthalate exposure and metabolism.

Keywords:

Biomonitoring Human skin uptake Skin penetration Skin permeation

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Area of Science:

Environmental Health
Toxicology
Dermatology

Background:

Widespread human exposure to phthalates necessitates understanding absorption routes.
Limited data exist on phthalate skin absorption, a key exposure pathway.
Phthalates are endocrine disruptors linked to various health concerns.

Purpose of the Study:

To characterize the in vitro skin permeation of di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP) in mixture.
To compare in vitro skin permeation data with in vivo urinary excretion in human volunteers.
To investigate the influence of formulation (neat vs. emulsion) on phthalate skin absorption.

Main Methods:

In vitro human skin permeation studies using flow-through diffusion cells over 24 hours.
Application of phthalate mixtures (neat and emulsion) to human skin samples.
Analysis of phthalate metabolites in receptor fluid and volunteer urine samples.
Comparison of in vitro permeation kinetics with in vivo urinary excretion patterns.

Main Results:

Phthalates permeated the skin barrier, metabolizing into monoesters.
Emulsion formulations significantly increased phthalate skin permeation compared to neat substances.
Diethyl phthalate (DEP) showed rapid permeation and early urinary excretion peak; dibutyl phthalate (DBP) showed slower kinetics and later peak; di(2-ethylhexyl) phthalate (DEHP) had minimal permeation.
In vitro results correlated well with in vivo urinary excretion data.

Conclusions:

Human skin is a significant route for phthalate absorption.
Formulation, particularly emulsions, impacts phthalate skin uptake.
In vitro models effectively predict in vivo phthalate absorption and metabolism kinetics.
Understanding skin absorption is crucial for developing effective phthalate exposure reduction strategies.