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625074 
Technical Report 
In vitro determinants of particulate toxicity: The dose-metric for poorly soluble dusts 
Faux, SP; Tran, CL; Miller, BG; Jones, AD; Monteiller, C; Donaldson, K 
2003 
Institute of Occupational Medicine 
United Kingdom 
154 
Rats exposed to high airborne mass concentrations of low toxicity poorly soluble particles (LTPSP) have developed lung disease such as fibrosis and lung cancer. These particles are regulated on a
mass basis in occupational settings. However, animal studies have shown ultrafine particles producing a stronger inflammatory effect than fine particles per unit mass. The present study investigated whether the surface area of LTPSP is a better descriptor than mass of their ability to stimulate pro-inflammatory responses in vitro. In a human alveolar epithelial type II-like cell line, A549, we measured interleukin-8 (IL-8) mRNA, IL-8 protein release and glutathione (GSH) depletion as markers of pro-inflammatory
effects and oxidative stress after treatment with a range of LTPSP (ultrafine and fine) and DQ12 quartz, a known cytotoxic dust In all the assays, ultrafine preparations of titanium dioxide [TiO2] and of
Carbon Black [CB] produced much stronger inflammatory responses than the same mass dose of fine TiO2 and CB.
The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultrafine metal dusts (cobalt and nickel) produced GSH depletion similar to ultrafine TiO2, with very similar surface areas. In all the assays, the fine and ultrafine CB produced a lower response than expected, given its high measured surface area. This may be because CB has a porous structure and therefore a very complex surface. As expected, DQ12 was more strongly inflammatory than the low toxicity dusts, on either a mass or surface area basis. Dose response relationships
observed in the in vitro assays appeared to be directly comparable to dose response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose
measured as surface area relative to the area of the exposed cells, at around 1 to 10 cm2/cm2.
This report and the work it describes were funded by the Health and Safety Executive (HSE). Its contents, including any opinions and/or conclusions expressed, are those of the authors alone and do
not necessarily reflect HSE policy.