Extracellular cadmium in the bronchoalveolar space of long-term tobacco smokers with and without COPD and its association with inflammation

Britt-Marie Sundblad,1,* Jie Ji,1,* Bettina Levänen,1 Klara Midander,2 Anneli Julander,2 Kjell Larsson,1 Lena Palmberg,1 Anders Lindén1 1Unit for Lung and Airway Research, 2Unit for Occupational and Environmental Dermatology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden *These authors contributed equally to this work Abstract: Tobacco contains cadmium, and this metal has been attributed a causative role in pulmonary emphysema among smokers, although extracellular cadmium has not to date been quantified in the bronchoalveolar space of tobacco smokers with or without COPD. We determined whether cadmium is enhanced in the bronchoalveolar space of long-term tobacco smokers with or without COPD in vivo, its association with inflammation, and its effect on chemokine release in macrophage-like cells in vitro. Bronchoalveolar lavage (BAL), sputum, and blood samples were collected from current, long-term smokers with and without COPD and from healthy nonsmokers. Cadmium concentrations were determined in cell-free BAL fluid using inductively coupled plasma mass spectrometry. Blood monocyte-derived macrophages were exposed to cadmium chloride in vitro. Depending upon the type of sample, molecular markers of inflammation were quantified either as protein (enzyme-linked immunosorbent assay) or as mRNA (real-time polymerase chain reaction). Cadmium concentrations were markedly increased in cell-free BAL fluid of smokers compared to that of nonsmokers (n=19–29; P<0.001), irrespective of COPD. In these smokers, the measured cadmium displayed positive correlations with macrophage TNF-α mRNA in BAL, neutrophil and CD8+ cell concentrations in blood, and finally with IL-6, IL-8, and MMP-9 protein in sputum (n=10–20; P<0.05). The cadmium chloride exposure caused a concentration-dependent increase in extracellular IL-8 protein in monocyte-derived macrophages in vitro. In conclusion, extracellular cadmium is enhanced in the bronchoalveolar space of long-term smokers and displays pro-inflammatory features. Its pathogenic role in tobacco-induced disease deserves further evaluation. Keywords: cigarette, metal, obstruction, macrophage, neutrophi

Reflections on the OECD guidelines for in vitro skin absorption studies

At the 8th conference of Occupational and Environmental Exposure of the Skin to Chemicals (OEESC) (16–18 September 2019) in Dublin, Ireland, several researchers performing skin permeation assays convened to discuss in vitro skin permeability experiments. We, along with other colleagues, all of us hands-on skin permeation researchers, present here the results from our discussions on the available OECD guidelines. The discussions were especially focused on three OECD skin absorption documents, including a recent revision of one: i) OECD Guidance Document 28 (GD28) for the conduct of skin absorption studies (OECD, 2004), ii) Test Guideline 428 (TGD428) for measuring skin absorption of chemical in vitro (OECD, 2004), and iii) OECD Guidance Notes 156 (GN156) on dermal absorption issued in 2011 (OECD, 2011). GN156 (OECD, 2019) is currently under review but not finalized. A mutual concern was that these guidance documents do not comprehensively address methodological issues or the performance of the test, which might be partially due to the years needed to finalize and update OECD documents with new skin research evidence. Here, we summarize the numerous factors that can influence skin permeation and its measurement, and where guidance on several of these are omitted and often not discussed in published articles. We propose several improvements of these guidelines, which would contribute in harmonizing future in vitro skin permeation experiments

Exposure media a critical factor for controlling dissolution of CuO nanoparticles

Dissolution is an important property that influences nanoparticle abundance and biological responses, and often becomes a critical factor in determining the safety of nanoparticles. In our study, the dissolution behavior of commercial (c-CuO) and synthesized CuO (s-CuO) nanoparticles, of size 31?�?4 nm and 7?�?1 nm, respectively, in a range of simulated aqueous media (artificial sea water, artificial lysosomal fluid, simulated body fluid, and 1 mM NaNO3) was assessed. The study demonstrated significant differences in the dissolution behavior of the nanoparticles based on the exposure concentration and exposure media. In biological media, both c-CuO and s-CuO demonstrated more than 80% dissolution within 12 to 24 h as compared to less than 15% dissolution in environmental media over the 7-day period. Due to the inherent size difference between c-CuO and s-CuO nanoparticles, the rate of dissolution was found to be higher in the case of s-CuO nanoparticles. To validate the role of dissolution, the microbial response of CuO nanoparticles and its ionic species was evaluated on E. coli. This study highlights the interplay between particulate and ionic form and experimentally validates how the suspension media acts as a critical factor governing the solubility of nanoparticles.by Swaroop Chakraborty , Ashwathi Nair, ManasPaliwal, Agnieszka Dybowska and Superb K.Misr