Table 4 Overview of genotoxicity outcomes obtained with crystalline silica of respirable size in animal or human studies

DQ12 (410 nm) milled to reach this small size

Intravenous injection (tail vein), at a dose of 100 mg/kg to rats as reference to compare to nanosize silicas and gold nanoparticles. Acute effects up to 48 h.

MN and comets were measured in lung, liver and blood after 4 h, 24 h and 48 h. All effects seen were consistent with a secondary genotoxic mechanism:

- No increased MN in circulating blood reticulocytes

- No increased comets in blood cells

- Increased plasma TNF-alpha

- Increased apoptosis and liver inflammation after DQ12

[17]

Quartz Q1 with mean size (D₅₀) of 12.1 μm. 0.89 m²/gram and DQ12 (D₅₀, 3 μm)) with or without different organosilane coatings (PTMO, SIVO 160) and aluminium lactate as control inhibitor

90-day rat study. Particles (total dose 1 mg/animal), administered by intratracheal instillation of two 0.5 mg aliquots in 0.3 ml of PBS on consecutive days. Lavage and histology on day 28 and day 90.

Q1 and DQ12 both induced a persistent inflammatory response at 28 and 90 days. Both toxicity and inflammatory response were reduced to control levels by organosilane coatings of Q1. In vivo genotoxicty responses were not included in this paper.

[23]

DQ12 (respirable), 6 mg total cumulative dose

Instillation (intratracheal) with 3 × 2 mg each month

Poly (ADP-ribose), 8-OH-dG and OGGG 1 induction were assessed in lung tissue using immunohistochemistry (IHC). A good correlation was found between all genotoxicity markers and histopathological inflammation

[29]

DQ12, single dose of 100 mg/kg)

C57BL/6 wild-type (WT) and p47^phox−/−mice; DQ12 administered by pharyngeal aspiration

In vivo oxidative DNA damage in lung tissue was not affected by quartz exposure and did not differ between p47phox− /− and WT mice.

Neutrophils from the bone marrow of DQ12-treated WT mice, but not from p47^phox−/− mice, caused increased oxidative DNA damage when co-cultured with A549 epithelial cells.

[31]

Occupational exposure to respirable silica (<  70% RCS)

Male workers (n = 50) exposed to RCS dust in grinding, milling, bagging and sandblasting. Life time exposure by inhalation. Control group (n = 29) were office workers.

Both target cells (nasal epithelial cells, NEC) and non-target cells (PBL) were isolated and tested for percentage of MN. Increased MN were found in NEC (3-fold) and PBL (2-fold) of workers versus controls.

A multiple regression analysis showed significant contribution of age, smoking and number of years exposure, particularly in workers’ target NEC but also in surrogate cells (PBL)

[32]