Concepts of Nanoparticle Dose Metric and Response Metric

摘要: Wittmaack (2007) did not agree with our suggestion (Oberdorster et al. 2005) that particle surface area is a more appropriate dose metric than mass or number when evaluating dose–response relationships of nanoparticle-induced pulmonary inflammation. According to his understanding nanotoxicology and based on calculations, he found work best as metric. Throughout review we pointed out the concept should be considered in context nanoparticle properties such chemistry, charge, coating, crystallinity, porosity, reactivity. For example, nano-titanium dioxide (TiO2) nano-copper particles, very distinct from one another, will predictively create separate well-fitting relationships. Yes, importance well, indicated review, but direct metric. We would like address some issues raised article. First, suggested expressing inflammatory response, response better done using ratio lavaged neutrophils (PMN; polymorphonuclear leukocytes) macrophages instead fraction PMNs. Because purpose was describe these responses mathematical terms (whether threshold, linear, nonlinear) rather illustrate basis—but basis—are different, choice irrelevant. To demonstrate this, present data again (Figure 1), expressed absolute numbers elicited PMNs PMN/macrophage ratios function administered 1A,B), 1C,D), 1E,F) fine ultrafine (nanosized) TiO2. The are essentially same those shown percentage neutrophils. Figure 1 Inflammatory cell lung lavage 24 hr after intratracheal instillation (~ 250 nm) (20–30 TiO2 by different metrics [particle (A,B), (C,D), (E,F)] ... Second, regarding issue being metric, 1B) several orders magnitude apart for TiO2, whereas plot 1C) shows good fit combined sizes. reviewers Wittmaack’s article apparently overlooked this flaw argument. Finally, calculated 77 m2/g 50 m2/g, reported 2005). He derived value basis specific density (anatase) spherical primary size 20 nm. BET (Degussa P25) has been measured independently investigators, including group (Jwo 2005; Long 2006; Wahl 2005), ranges between 48 55 m2/g. There no reason mathematically manipulate completely at odds actual measurements. In contrast well-established area, average firmly established, values 20–30 Indeed, 30 nm (calculated 51.2 m2/g) conforms surface. Thus, added Figure 1C 1D; order difference particles obvious, regardless whether ultrafines size. We have concluded three discussed, worst effects.