Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison

Nanotoxicology. 2016 Oct;10(8):1188-202. doi: 10.1080/17435390.2016.1202348.

Abstract

Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs.

Keywords: Antigen presentation; development; immunotoxicity; metabolism; reproduction; single walled-carbon nanotubes.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects*
  • Antigen-Presenting Cells / immunology
  • Apoptosis / drug effects
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cell Cycle / drug effects
  • Cytokines / immunology
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / toxicity*
  • Female
  • Instillation, Drug
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nanotubes, Carbon / chemistry
  • Nanotubes, Carbon / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / immunology*
  • Reproduction / drug effects*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Toxicity Tests / methods

Substances

  • Cytokines
  • Environmental Pollutants
  • Nanotubes, Carbon