Semi-volatile organic compounds (SVOCs) are present in a plethora of professional and household products (i.e., pesticides, cosmetics, plasticizers, floor coverings and furnishings). Several SVOCs have shown endocrine disrupting effects and are labeled as chemicals of concern. They are often present in the indoor environment where adults spend an estimated 19 to 21 hours a day. SVOCs are mainly found in the air as aerosols and settled on dust particles. Although inhalation is an important route of exposure, there is a lack of human studies to understand SVOCs toxicokinetics. The reason is the absence of reliable techniques for measuring the inhaled dose and practical device for use with human participants Our pilot study is the first step to fill this gap. We optimized an aerosol delivery system (ADS) for SVOCs to generate known inhalation exposures. Our first study objective was to assess the feasibility of recruiting participants for a repeated inhalation SVOC exposure over a period of one week with the ADS. The second objective was to improve an experimental design for future comprehensive toxicokinetic study in participants. Our chosen model SVOC was di(2‐ethylhexyl) phthalate (DEHP). Ring-deuterated DEHP (DEHP-d4) was used to differentiate the experimental exposures to DEHP from environmental contaminations. Occupational exposure limits (OELs) are time-weighted average air concentrations of hazardous substances for which workers can be repeatedly exposed (8-hour workday and 40-hour workweeks) for a working lifetime without adverse effects. The exposure dose in our study was calculated (0.45 mg/week) after quantification of DEHP-d4 in the generated aerosol and set below the Swiss OEL for DEHP. Participants (N=4) used the ADS with DEHP-d4 at home twice daily (morning and evening; 40 puffs in 10 minutes) for four days. Urine samples were collected before exposure (day 1), and then four times per day (upon waking, at noon, late afternoon and at bedtime) the rest of the study week. Four urinary DEHP-d4 metabolites were quantified: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP).
The participants reported that the optimized ADS was easy-to-use and that the study protocol was understandable. Labelled metabolites were successfully found in the urine samples following the DEHP-d4 exposure concentration. The metabolite concentrations increased over the exposure week indicative of a possible accumulation. This pilot study shows that future toxicokinetic studies with healthy participants can be conducted with controlled exposures to SVOCs using this optimized aerosol delivery system.