Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison.
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.
a Myunggok Eye Research Institute, Konyang University , Daejeon , Republic of Korea .
Eun-Jung
EJ
Park
b Department of Molecular Science and Technology , Ajou University , Suwon , Republic of Korea .
Je
J
Choi
b Department of Molecular Science and Technology , Ajou University , Suwon , Republic of Korea .
Jae-Ho
JH
Kim
c Toxicologic Pathology Center, Korea Institute of Toxicology , Daejeon , Republic of Korea .
Byoung-Seok
BS
Lee
d Seoul Center, Korea Basic Science Institute , Seoul , Republic of Korea , and.
Cheolho
C
Yoon
e Department of Chemical Engineering , Kwangwoon University , Seoul , Republic of Korea.
Uiseok
U
Jeong
e Department of Chemical Engineering , Kwangwoon University , Seoul , Republic of Korea.
Younghun
Y
Kim
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D007322:Instillation, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000139:chemically induced* / Q000276:immunology*; D012098:Reproduction / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018675:Toxicity Tests / Q000379:methods
D016207:Cytokines; D004785:Environmental Pollutants; D037742:Nanotubes, Carbon
Antigen presentation; development; immunotoxicity; metabolism; reproduction; single walled-carbon nanotubes