Abstract
BackgroundGrowing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up.MethodsHere, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m3) and Low (< 0.1 µg/m3) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance.ResultsIn total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q2 = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers.ConclusionsThe serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.Graphical abstract
Highlights
Use of carbon nanotubes and nanofibers (CNT/F) continues to grow across multiple industries, from aerospace, automotive, and electronics to healthcare and the life sciences [1]
CNT/F occupational exposure induced a significant and diverse peptidomic response in the blood In this study, the serum peptidome was assessed for 24 workers at CNT/F facilities who were not active smokers and reported no active respiratory disease
All three CNT/F exposure metrics were significantly greater for the High relative to the Low exposure groups (Table 1): inhalable elemental carbon (EC), Kruskal Wallis H = 17.28, p < 0.001; respirable EC, H = 17.28, p < 0.001; CNT/F structure counts, H = 6.16, p = 0.013
Summary
Use of carbon nanotubes and nanofibers (CNT/F) continues to grow across multiple industries, from aerospace, automotive, and electronics to healthcare and the life sciences [1]. Their unique physicochemical properties make CNT/F attractive for a variety of Mostovenko et al Part Fibre Toxicol (2021) 18:39 manufacturing needs; the recent growth in their use presents unknown occupational health hazards. The CNT/F toxicological profile is influenced by workplace determinants such as environmental conditions, worksite mitigation, and protective equipment measures Such factors were moderately predictive of CNT/F exposure [16], though cannot inform on the in vivo biological response. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up
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