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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Immunomodulatory properties of multi-walled carbon nanotubes in peripheral blood mononuclear cells from healthy subjects and allergic patients
Author:
Laverny G, Casset A, Purohit A, Schaeffer E, Spiegelhalter C, de Blay F, Pons F
Year:
2013
Bibliographic source:
Toxicol Lett., 217(2):91-101

Materials and methods

Endpoint addressed:
immunotoxicity
Principles of method if other than guideline:
Investigation of the immunomodulatory activity in peripheral blood mononuclear cells (PBMCs) from healthy donors and mite-allergic subjects.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tangled Multi-Walled Carbon Nanotubes
EC Number:
701-160-0
Cas Number:
7782-42-5
Molecular formula:
Hollow tubular carbon, 1-dimensional nano structures with hexagonal arrangement of carbon atoms
IUPAC Name:
Tangled Multi-Walled Carbon Nanotubes
Constituent 2
Reference substance name:
GRAPHISTRENGTH C100
IUPAC Name:
GRAPHISTRENGTH C100
Test material form:
solid: nanoform

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
PBMCs from healthy donors and mite-allergie subjects were stimulated wlth Toll-like receptor (TLR) agonists, a T cell mitogen and/or a specific allergen to characterize the potency of MWCNTs to modulate innate and adaptive Immune response. Mixed lymphocyte reactions (MLRs) were performed with allogeneic PBMCs from healthy donors to further study the impact of MWCNTs on T cell activation. As well, differentiation, maturation and function of monocyte-derived dendritic cells (MDDCs) were assessed in the presence or absence of MWCNTs, to provlde information on whether MWCNTs preferentially target antigen-presenting cells (APCs).

Results and discussion

Applicant's summary and conclusion

Executive summary:

The immunomodulatory activity of Graphistrength C100 was investigated in peripheral blood mononuclear cells (PBMCs) from healthy donors and mite-allergic subjects. Freshly prepared PBMCs, stimulated or not with Toll-like receptor (TLR)1-9 agonists, a T cell mitogen (phytohemagglutinin A) or mite allergen extract were cultured in the presence or absence of MWCNTs. Secretion of TNF-a, IL-2, IL-5, IL-6, IL-12/23p40 or IFN-¿was quantified in the culture supernatants by ELISA. Basal secretion of all the cytokines was not altered by MWCNTs in PBMCs from both healthy donors and allergic subjects. In PBMCs from healthy donors, TNF-a, IL-6 and IL-12/23p40 secretion in response to the TLR4 agonist, lipopolysaccharide was however increased in a dose-dependent manner by MWCNTs. Significant increases in the release of these cytokines were also observed in PBMCs stimulated with a TLR2 or TLR3 agonist. MWCNTs also increased the release of IL-2 and IFN-¿by PBMCs stimulated with a T cell mitogen. In contrast, MWCNTs inhibited allergen-induced IL-5 secretion by PBMCs from mite-allergic subjects. As well, MWCNTs altered the capacity of PBMC-derived monocytes to differentiate into functional dendritic cells. All together, these data suggest that according to its immune cell target, MWCNTs may either promote or suppress immune responses in humans. Further investigations are necessary to fully understand the complexity behind interactions of engineered nanoparticles with the immune system.

According to the available data, no translocation ofGraphistrength C100 to the circulating blood is expected after an inhalation exposure. Therefore this potential effect on the peripheral blood mononuclear cells observed in these in vitro conditions is not expected to occur in vivo.