Journal of Nanomaterials

Review Article

Human Biomonitoring of Engineered Nanoparticles: An Appraisal of Critical Issues and Potential Biomarkers

Table 1

Biomarkers of exposure and effect potentially available for human biomonitoring studies assessing exposure-effect relationships between particulate matter/ultrafine particles and health effects. In bold are listed the more promising biomarkers (e.g., validated in human studies on people exposed to different ultrafine or fine particulates or known fractions), whereas in italic are reported some potential biomarkers. Legend: EBC: Exhaled Breath Condensate; MDA: Malondialdehyde; T-BARS: Thiobarbituric Acid Reactive Substances; LTB₄: Leucotriene-B₄; NO: Nitric Oxide; 8-OH-dG: 8-hydroxy-2^′-deoxyguanosine; 8-oxo-Gua: 8-oxo-7,8-dihydroguanine; 4-HNE: 4-hydroxy-2-nonenal; CC16: Clara Cell protein; hsCRP: high sensitivity C-reactive protein; IL-6: plasma Interleukin 6; sTNF-RII: soluble Tumor Necrosis Factor-receptor II; PAI-1: plasminogen activator inhibitor-1; V-CAM: vascular adhesion molecule; FPG-ENDOIII: lesions detected as sites in DNA sensitive to formamidopyrimidine DNA glycosylase and endonuclease III.


Exposure	Effective dose/early effect	Altered structure/function

(i) Exhaled particles in EBC (“deposited dose”)	(i) Lipid peroxidation products in EBC or blood (MDA, T-BARS, conjugated dienes, LTB₄, F2- and 8-isoprostane)	(i) Fibrogenic markers
(ii) Circulating particles	(ii) Oxidatively damaged DNA (8-OH-dG, 8-oxo-Gua)	(ii) Cell transformation assays
(iii) Particle uptake by specialized cells (e.g., macrophages)	(iii) Exhaled NO and nitrosative stress products (3-nitrotyrosine)	(iii) Micronucleus
(iv) Elemental analysis (for metallic NM, e.g., metal oxides) in biological fluids	(iv) Carbonyl compounds (4-HNE) in EBC	(iv) DNA strand breaks (Comet assay + FPG-ENDO III)
(v) Protein modification (“corona”)	(v) Serum pneumoproteins (CC16)	(v) DNA hypomethylation
	(vi) Platelet activation/aggregation and prothrombotic changes	(vi) MicroRNAs (miRNAs)
	(vii) Acute phase proteins (hsCRP), IL-6, and sTNF-RII
	(viii) Clotting factors (fibrinogen, PAI-1), blood microparticles
	(ix) Tissue factor (TF) activity in plasma
	(x) Vascular adhesion molecules (V-CAM-1)
	(xi) Upregulation of GPIIb/IIIa in platelets