Repeated Human Exposure to Semivolatile Organic Compounds by Inhalation: Novel Protocol for a Nonrandomized Study

Area of Science:

• Environmental Health
• Toxicology
• Human Exposure Science

Background:

• Semivolatile organic compounds (SVOCs), including phthalates, are common additives in consumer products.
• SVOCs can become airborne as aerosols, posing potential health risks, particularly endocrine disruption from phthalates.
• Limited human data exists on the absorption, distribution, metabolism, and excretion (ADME) of inhaled SVOCs.

Purpose of the Study:

• To develop and validate a novel method for controlled, repeated inhalation exposure to SVOCs in humans.
• To characterize the ADME of phthalates following inhalation exposure.

Main Methods:

• A portable device was developed to generate isotope-labeled diethylhexyl phthalate (DEHP-d4) aerosols for home-based inhalation.
• Participants (n=10) undergo repeated short daily exposures over 4 days at concentrations below occupational exposure limits.
• DEHP-d4 and its metabolites are quantified in blood and urine samples collected before, during, and after exposure.

Main Results:

• The developed device successfully generates DEHP-d4 aerosols with particle diameters ≤2.5 μm.
• The device delivers a mean DEHP-d4 mass of 1.4 (SD 0.2) μg per puff.
• Five participants have been enrolled in the study as of May 2023.

Conclusions:

• A portable aerosol-generating device is effective for phthalate exposure in human studies.
• This method facilitates human ADME characterization of inhaled SVOCs.