Toxicology of glycol ethers: systemic and pulmonary assessment

Glycol ethers, primarily used as solvents, represent a global market of several million tonnes and are found in a wide range of consumer goods for domestic and professional use (e.g., paints, adhesives, cosmetics, cleaning products). The general population is chronically exposed to glycol ethers via inhalation, particularly to those derived from propylene glycol ethers, which dominate the market.

The human toxicity of these compounds is still poorly studied, making it difficult for regulators to establish appropriate monitoring measures and usage guidelines. However, some studies report respiratory effects and changes in blood parameters in workers exposed to these substances.

Objectives

The primary aim of this research project is to assess potential respiratory changes in healthy participants exposed to two of the most widely used propylene glycol ethers derivatives. Participants are exposed to low and controlled concentration of each substance in a dedicated exposure chamber. Blood and urine samples are collected to determine internal dose and the blood elimination kinetics of the substances, as well as blood gas measurements. Pulmonary function tests are performed to detect possible alterations in the alveolar-capillary blood gas diffusion. These parameters are evaluated before exposure as a baseline (control), then during and after exposure, allowing each participant to serve as their own control.

In the second part of the project, human pulmonary cells (a sophisticated 3D model) are exposed for 6 and 24 hours to these propylene glycol ether derivatives via aerosolization using the Vitrocell Cloud system.

The goal of this part of the project is to assess:

• Cytotoxicity
• Integrity of the transepithelial barrier
• (Pro)-inflammatory responses
• Effect on surfactant tension

The cytotoxicity of glycol ethers will be tested at five different concentrations, covering a full range from no effect (0%) to total cytotoxicity (100%). Other biological responses will be assessed using a single concentration chosen based on cytotoxicity results (sub-toxic level) and the exposure concentration used in the human respiratory part of the study involving healthy volunteers.