Comparing human respiratory adverse effects after acute exposure to particulate matter in conventional and particle-reduced swine building environments.

OBJECTIVES: To evaluate innate immunity responses, lung function and symptoms in volunteers acutely exposed to organic dust in swine buildings after installing particle separators aimed to reduce particulate matter exposure. METHODS: 11 healthy participants were exposed in 2 different facilities, with and without installed particle separators, in a cross-over design including 2-3 weeks wash-out between the 2 exposures. Size, distribution and composition of particulate matter and endotoxins in the air were measured. Lung function (spirometry), bronchial responsiveness, symptoms questionnaire and markers of innate immunity in blood and nasal lavage were measured before and after the 3-hour exposures. RESULTS: The number of particles, in particular fine particles sized 0.3-0.5 µm, was reduced in the particle-separated swine building environment (PSE) compared with that in the conventional building (CE). In the PSE, headache (p=0.03) and increased body temperature (p=0.016) were less pronounced than in the CE. The expression of toll-like receptors (TLR)2 and TLR4 on blood monocytes significantly increased (p=0.016 and 0.017, respectively) while cluster of differentiation (CD)14 on neutrophils decreased (p=0.05) after exposure in the CE, yet with no difference between the 2 exposures. Compared with the conventional environment, exposure to the PSE yielded lower interleukin (IL)-6 (p=0.02) and IL-8 (p=0.04) levels in the upper respiratory tract, as assessed by nasal lavage. CONCLUSIONS: Particulate matter and organic dust in the swine building were reduced after installing particle separators, which, in naïve never exposed volunteers, in turn reduced adverse health effects caused by acute exposure in swine buildings compared with exposure to the conventional swine building environment.

A consistent and transparent approach for calculation of Derived No-Effect Levels (DNELs) for petroleum substances.

The REACH legislation introduced Derived No-Effect Levels (DNELs) which are defined as 'the levels of exposure above which humans should not be exposed'. DNELs were required for several categories of petroleum substances and CONCAWE developed a consistent approach for their derivation. First, the No-Observed Effect Level from a relevant study was corrected for pattern and route of exposure to obtain a modified Point-of-Departure (POD(modified)). Subsequently, the DNEL was calculated by dividing the POD(modified) by Assessment Factors (AFs) to adjust for inter- and intraspecies differences. If substance-specific information allowed, Informed Assessment Factors (IAFs), developed by CONCAWE were utilised. When little or no substance-specific information on those differences was known, default AFs from the guidance provided by ECHA were used. Some hazard endpoints did not lend themselves to calculation of DNELs (e.g. aspiration, dermal irritation, mutagenicity). DNEL calculation was considered not appropriate if adverse effects were not observed in tests conducted at a limit dose or if meaningful dose-response curves could not be developed. However, DNELs were calculated when hazards were identified, regardless of whether or not risk characterisation was required under REACH. Examples for gasoline, Lubricating Base Oils, gas oils and bitumen are provided to illustrate CONCAWE's approach.

Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles.

BACKGROUND: Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents. METHODS: In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6-10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system. RESULTS: Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM. CONCLUSION: This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.