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

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.