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

JMIR Res Protoc. 2023 Oct 13:12:e51020. doi: 10.2196/51020.


Background: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent.

Objective: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans.

Methods: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure.

Results: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 μm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) μg per puff (n=6). As of May 2023, we have enrolled 5 participants.

Conclusions: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies.

International registered report identifier (irrid): DERR1-10.2196/51020.

Keywords: DEHP; SVOCs; diethylhexyl phthalate; healthy participants; inhalation exposure; phthalates; portable aerosol-generating device; protocol; semi-volatile organic compounds; toxicokinetics study; toxicology.