Acute aspiration of graphene sheets evokes transient airway hyperreactivity to methacholine in mice (660.4)

Abstract

Concern exists that the use of graphene sheets (GS) in composite materials might expose manufacturing workers to an inhalation hazard. Studies have shown that GS are cytotoxic in vitro (PC12 cells, fibroblasts) and in vivo in mice (lung granuloma), and Roberts et al. (2013) found non‐oxidized GS with larger lateral dimensions (蠅 5 μm) and a greater number of layers (~20) produced more lung inflammation up to 7 d after aspiration in mice when compared to smaller GS (<1 μm laterally, ~ 4 layers). The lung toxicity of various forms of GS has not been characterized completely. Here, we investigated the effects of GS on basal lung resistance (RL), basal dynamic compliance (CDyn), and reactivity to inhaled methacholine (MCh) aerosol. Mice were given a non‐oxidized GS (5 μm x 5 μm laterally, 7 nm thick equal to ~ 20 layers; 40 µg) suspended in dispersion medium (DM; Porter et al., 2008) or DM (control) via aspiration. RL and CDyn and reactivity to increasing concentrations of MCh aerosol were measured 4 h ‐ 2 mo after GS exposure. Basal RL was increased 4 h post‐exposure but at no other time; basal CDyn was unaffected at any time. Airway reactivity to MCh (as ΔRL) was increased at 4 h post‐exposure, and ΔCDyn responses were decreased. GS was essentially without effect on RL or CDyn at 1 d, 1 wk, 1 mo and 2 mo after administration. The results indicate that a single exposure to GS increases transiently lung resistance and reactivity to MCh.Grant Funding Source: Supported by NIOSH