Toxicological Effects of Metal Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 199

TABLE 9.2
Comparison of in Vitro and in Vivo (Instillation) Effects of Various Types of
Silver Nanoparticles, Compared to Benchmark Metal Oxide Nanoparticles
(See Also Chapter 8)

Ag50.
EO

Ag5.
PVP

Ag200.
PVP

Ag50.
citrate

ZrO 2
acryl

ZnO
NM110

TiO 2
NM105

In vivo
instillation

mg per rat
lung

0.6 0.6 0.6 0.6 0.6

BALF AM (3 days) ++ +/− +++ +

AM (21 days) +++ ++ ++ +/−

PMN (3 days) ++++ ++++ ++++ +

PMN (21
days)

++++ ++ ++++ +/−

NP in AM y y y y n.o.

Free
agglomerates

n n n y n

Histology Local necrosis y y y y n

Particles in
AM

y y y y n.o.

NP in tissue
AM

y y y y y

In vitro
macrophages

pg/cell 1.9-45 1.9-45 1.9-45 1.9-45 15-120

LDH ++++ +++ ++ + +

LOAEL (pg/
cell)

1.9-3.8 7.5-15 >30 15-30 30 3.8-7.5 30-60

LOAEL (µg/
mL)

2.8-5.6 11.3-22.5 >45 22.5-45 45 5.7-11.3 45-90

Abbreviations: AM, alveolar macrophages; PMN, granulocytes; LDH, lactate dehydrogenase; LOAEL,

low observed effect level; +/−, +, ++, +++, ++++, no, small, moderate, large, or excessive
effect; n, no; y, yes; n.o., likely but not directly observable due to weak contrast.

(LDH) and glucuronidase the following ranking of cytotoxicity was obtained:
Ag50.EO > Ag50.PVP > Ag50.citrate > Ag200.PVP. In general, all effects could
be attributed to the presence of particles because particle-free supernatants evoked
no apparent cytotoxicity. Significant cytotoxic effects of silver NPs started in the
low micro-molar range, but differed with respect to surface coating (Table 9.2).
Interestingly, Ag50.citrate at nontoxic concentrations induced more TNFα than
all other tested Ag NPs, suggesting a “particle-to-cell-surface” mediated effect
(M. Wiemann and A. Venneman, unpublished observation).

9.4 in ViVo TOXICITY OF METAL NANOMATERIALS
The in vitro studies can act as a prescreening for nanoparticles with biological
effects but they cannot simulate the complexity of a human organ. A reliable hazard