Figure 4

Comparison of effects among studies of inhalation exposure to multi-walled carbon nanotubes (MWCNT). Cumulative MWCNT exposures (concentration (C) x time (T) – mg/m³ multiplied by total hours of exposure) were plotted on a logarithmic scale from studies that exposed rodents by inhalation to various doses of MWCNT (black circles). Measured toxicologic endpoints were identified for each cumulative exposure. Symbols represent histopathologic alterations (*), increased bronchoalveolar lavage (BAL) polymorphonuclear cell (PMN) influx or enzyme activity ($), increased BAL total protein or albumin (^), increased tissue or BAL cytokines (@), and alterations in mRNA expression (&). The lack of a symbol means either the endpoint was not measured or there was no effect due to treatment. Symbols in parantheses indicate either a transient effect, the effect was scored as minimal, or the response was not consistently measured at all post-exposure time points for that given cumulative C x T. Each of the 5 toxicologic endpoints were highlighted by an arbitrary cutoff (dashed lines) to illustrate the threshold cumulative C x T to result in significant pulmonary responses in general agreement across various study designs. The numbers representing the dashed lines are as follows: 5 – histological alterations, 4 – increased BAL PMN influx or enzyme activity, 3 – increased BAL total protein or albumin, 2 – increased tissue or BAL cytokines, and 1 – alterations in mRNA expression. The years indicated on the left side of the graph are the extrapolations of the mouse lung burden from this study to represent years of worker exposure to an inhalable elemental carbon concentration of 10.6 μg/m³ assuming 25% respirability which predicts a MMAD of 5.5 μm.