Intravenous administration of three multiwalled carbon nanotubes to female rats and their effect on urinary biochemical profile.

ABSTRACT

This study was conducted to investigate the influence of outer diameter (OD) and length (L) of multiwalled carbon nanotubes (MWCNTs) on biodistribution and the perturbation of endogenous metabolite profiles. Three different-sized carboxylated MWCNTs (NIEHS-12-2 L 0.5-2 µm, OD 10-20 nm, NIEHS-13-2 L 0.5-2 µm, OD 30-50 nm, and NIEHS-14-2 L 10-30 µm, OD 10-20 nm) in water were administered to female Sprague-Dawley rats as a single intravenous dose of 1 mg/kg MWCNTs. Biodistribution in liver, lung, spleen, and lymph nodes was evaluated in tissue sections at 1 and 7 days' post-dosing using enhanced darkfield microscopy and hyperspectral imaging. Nuclear magnetic resonance (NMR) analysis was used for biochemical profiling and pathway mapping of endogenous metabolites in urine collected at 24-h intervals prior to dosing, at Day 1 and Day 7. At Day 1 and Day 7, all three MWCNTs were observed in liver. NIEHS-12-2 was observed in spleen, whereas NIEHS-13-2 and NIEHS-14-2 were not. All three MWCNTs were observed in lymph nodes and lung at Day 7. The urinary biochemical profile showed the highest positive fold change (FC) at Day 7 for the metabolites acetate, alanine, and lactate, whereas 1-methylnicotinamide, 2-oxoglutarate, and hippurate had some of the lowest FCs for all three MWCNTs. This study demonstrates that the observed tissue location of MWCNTs is size dependent. Overlaps in the perturbation of endogenous metabolite profiles were found regardless of their size, and the biochemical responses were more profound at Day 7 compared with Day 1, indicating a delayed biological response to MWCNTs.