Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Although chronic toxicity of multiwalled carbon nanotube (MWCNT) has been a critical issue in the field of nanotoxicology for over a decade, there has been only one 2-year inhalation study assessing pulmonary carcinogenicity of MWNT-7 in rats by Kasai et al.. In another 2-year study, rats administered MWNT-7 by repeated intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. This differences in the 2 studies could be attributed to the difference in the temporal pattern of MWNT-7 lung burden, i.e., continuous exposure by inhalation results in increasing lung burden throughout the experimental period, while the protocol of the intratracheal instillation results in maximal the lung burden at the beginning of the study period.
We recently implemented 2 intermittent exposure studies in which we administered MWNT-7 by intratracheal instillation with 4-weeks intervals for more than 1 year, allowing lung burdens of MWNT-7 to gradually increase, similar to the inhalation study. A 2-year treatment of MWNT-7 resulted in the significant increases of the incidences of lung tumors and pleural mesotheliomas. In another experiment, a shortened MWNT-7 (pretreated by a grinder) was administered for 1 year with a subsequent 1-year non-treatment period. No lung tumors were observed; however, pleural mesotheliomas were sporadically found through the exposed groups. These suggest that the temporal pattern of the lung burden, the structure of MWCNT, and the exposure methods can affect the outcomes of carcinogenicity tests.
