Needlelike, short and thin multi-walled carbon nanotubes: comparison of effects on wild type and p53^+/− rat lungs

Abstract

Carbon nanotubes (CNTs) are nanomaterials presenting an occupational inhalation risk during production or handling. The International Agency for Research on Cancer classified one CNT, Mitsui-7 (MWNT-7), as ‘possibly carcinogenic to humans’. In recognition of their similarities, a proposal has been submitted to the risk assessment committee of ECHA to classify all fibers with ‘Fibre Paradigm’ (FP)-compatible dimensions as carcinogenic. However, there is a lack of clarity surrounding the toxicity of fibers that do not fit the FP criteria. In this study, we compared the effects of the FP-compatible Mitsui-7, to those of NM-403, a CNT that is too short and thin to fit the paradigm. Female Sprague Dawley rats deficient for p53 (GMO) and wild type (WT) rats were exposed to the two CNTs (0.25 mg/rat/week) by intratracheal instillation. Animals (GMO and WT) were exposed weekly for four consecutive weeks and were sacrificed 3 days or 8 months after the last instillation. Exposure to both CNTs induced acute lung inflammation. However, persistent inflammation at 8 months was only observed in the lungs of rats exposed to NM-403. In addition to the persistent inflammation, NM-403 stimulated hyperplasic changes in rat lungs, and no adenomas or carcinomas were detected. The degree and extent of hyperplasia was significantly more pronounced in GMO rats. These results suggest that CNT not meeting the FP criteria can cause persistent inflammation and hyperplasia. Consequently, their health effects should be carefully assessed.

Keywords:

• MWCNT
• p53^+/- rats
• intratracheal instillation
• hyperplasic changes
• lung

Acknowledgements

The authors gratefully acknowledge Sylvie Michaux, Laurine Douteau, and Aline Dosen for animal care and husbandry, Anne-Marie Lambert-Xolin and Philippe Marsan for biochemical analyses, Stéphane Grossmann and Claire Seiwert for technical assistance, Isabelle Langonné and Samuel Muller for micronuclei analyses, and Aurélie Remy for statistical analyses. Slides for histological analyses were expertly prepared by Sauli Savukoski.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The transcriptomic data are available in the GEO repository under accession number GSE214574 (http://www.ncbi.nlm.nih.gov/geo/)

Additional information

Funding

This study was funded by the National Fund for the Prevention of Occupational Accidents and Diseases.