Bio: Professor Flemming R. Cassee is an inhalation toxicologist and Chief Science Officer at the Netherlands National Institute for Public Health and the Environment–RIVM. In this position, he is involved in research into adverse health effects from air pollution including fine particulate matter and microplastics) and airborne nanomaterials and particulate matter (fine dust as part of air pollution) and is directing the RIVM’s internal R&D programme. In addition to this, Flemming Cassee is professor of inhalation toxicology at the Institute of Risk Assessment Sciences of the Utrecht University, the Netherlands.

Abstract: We conducted a nose-only inhalation study of (MJO II) oil-fumes in mice, following the OECD 412 guideline. C57BL/6N mice were exposed to fumes generated by a Bleed-Air-Contamination Simulator (BACS) for 20 days at a nominal concentration of 15 mg/m³. Three dose groups (high, mid, and low) were exposed for varying durations, with a clean air control group and a diesel exhaust benchmark group. Two cohorts were studied: one sacrificed within 24 hours for sub-acute effects, and another 8 weeks later for long-term effects. Oil fume exposure resulted in only subtle behavioural effects in high-dose females, including transient changes in body weight and gait stability. No behavioural effects were observed in high-dose males or mid-dose animals. Importantly, oil fume exposure did not induce lung inflammation or particle accumulation in any dose group, unlike diesel exhaust. No neuroinflammation was detected in any oil fume dose group.  Summarizing the effects of oil fume exposure, behaviourally we only observed a subtle transient effect on body weight at exposure onset and very subtle effects on gait stability in the females of the HD group. There were no behavioural effects on HD males or animals of either sex in the MD group. There were also no indications of inflammation or tissue damage in the lung or neuroinflammation in the brain in any dose group or sex. Based on these results, the high dose (nominal concentration of 15 mg/m³ for 240 min/day) could be considered the No-Observed-Adverse-Effect Level (NOAEL) for male mice and the Lowest-Observed-Adverse-Effect Level (LOAEL) for female mice upon sub-acute inhalation exposure to BACS-generated oil fumes.

Abstract: Everybody is exposed to aerosols that consist of solid particles and fibres as well droplets. Those with an aerodynamic diameter less than 10 micrometre can be inhaled by humans. Knowledge on the tissue-specific internal dose of particles and fibres provides a critical link between individual external exposure (concentration) and toxicity (health effects). The deposition occurs primarily by impaction, diffusion and secondarily by thermophoretic effects during inhalation and exhalation. Fibres (asbestos, carbon nanotubes, polymers) and platelets like graphene can also be deposited in the lower respiratory tract, mainly by interception due to their small size and elongated shape.

Once deposited the chemical composition including surface reactivity and dissolution rates are the driving forces for toxicity. Often, the toxicity is driven by oxidative stress leading to inflammatory responses and tissue damage as well as lung cancer including mesothelioma related to persistent fibres. Particles can be translocated to other organs including the blood where they can also lead to adverse health outcomes.  In this section all aspect that have a profound impact on the dose and dose rate of inhaled particles and fibres will be discussed. Computer models to calculate the dose in various species including the humans as well as models to calculate the dose in in vitro submerged cell culture models will be discussed. This will be further illustrated by a tutorial to obtain hands on experience.