Lung Damage in Mice after Inhalation of Nanofilm Spray Products: The Role of Perfluorination and Free Hydroxyl Groups

Exposures to two commercial nanofilm spray products (NFPs), a floor sealant (NFP 1) and a coating product for tiles (NFP 2), were investigated for airway irritation, airway inflammation, and lung damage in a mouse inhalation model. The particle exposure was characterized by particle number, particle size distribution, and gravimetric analysis. BALB/cJ mice were exposed for 60 min to the aerosolized products at 3.3–60 mg/m3 (105–106 fine particles/cm3) measured in the breathing zone of the mice. Lung inflammation and lung damage were assessed by study of bronchoalveolar lavage fluid (BALF) cytology, protein in BALF, and histology. Mass spectral analysis showed that NFP 1 and NFP 2 contained hydrolysates and condensates of a perfluorosilane and alkylsilane, respectively. NFP 1 induced a concentration-dependent decrease of the tidal volume lasting for at least 1 day. Exposure concentrations above 16.1 mg/m3 (2.1 × 106 fine particles/cm3) gave rise to significant increases of protein level in BALF and reduced body weight, and histological examination showed atelectasis, emphysema, and hemorrhages. A narrow interval between the no-effect level (16.1 mg/m3) and the lethal concentrations (18.4 mg/m3) was observed. The alkylsilane-based product (NFP 2) had no effect at the concentrations studied. Experiments with different types of perfluorinated silanes and alkylsiloxanes showed that the toxic effects did not arise solely from the perfluorination. The number of free hydroxyl groups in the silanes/alkylsiloxanes was also critical for the toxicity

Analysis of arterial intimal hyperplasia: review and hypothesis

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it "benign intimal hyperplasia". However, normal or "benign " intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi