Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats.
The present study assessed a carcinogenic hazard of multi-wall carbon nanotube (MWCNT) in intact (not genetically modified) rodents. MWCNT (1 mg/kg body weight, 7 animals), crocidolite (2 mg/kg body weight, 10 animals) or vehicle (2% carboxymethyl cellulose, 5 animals) was administered to male Fischer 344 rats (12 weeks old) by a single intrascrotal injection. Rats were autopsied immediately after death, when becoming moribund or at the end of the maximal observation period scheduled to be 52 weeks. After 37-40 weeks, however, 6 MWCNT-treated animals died or became moribund due to intraperitoneally disseminated mesothelioma (6/7, 85.7%) with bloody ascites. Peritoneal mesothelium was generally hypertrophic, and numerous nodular or papillary lesions of mesothelioma and mesothelial hyperplasia were developed. While mesothelioid cells were predominant in relatively early stage tumors, advanced stage mesotheliomas were constituted by 2 portions occupied by mesothelioid cells on the surface and spindle-shaped sarcomatous cells in the depth. In the latter, the histological transition was apparently observed between these 2 portions. Mesotheliomas were invasive to adjacent organs and tissues, and frequently metastasized into the pleura. Only 1 rat survived for 52 weeks in the MWCNT-treated group, and similar findings except mesothelioma were observed. All 10 crocidolite-treated and 5 vehicle-treated rats survived for 52 weeks without any particular changes except deposition of asbestos in the former case. It is thus indicated that MWCNT possesses carcinogenicity causing mesothelioma at a high rate in intact male rats under the present experimental conditions. The present data identifies a carcinogenic hazard of MWCNT and will serve as one of the indispensable evidences to be used for the risk assessment crucial for not only protection and improvement of human health and welfare, but also safe and acceptable development and prevalence of this and similar upcoming materials.
Sakamoto
Yoshimitsu
Y
Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, Tokyo Metropolitan Institute of Public Health, Shinjuku, Tokyo, 169-0073, Japan. yoshimitsu_sakamoto@member.metro.tokyo.jp
Nakae
Dai
D
Fukumori
Nobutaka
N
Tayama
Kuniaki
K
Maekawa
Akihiko
A
Imai
Kiyoshi
K
Hirose
Akihiko
A
Nishimura
Tetsuji
T
Ohashi
Norio
N
Ogata
Akio
A
D000740:Anemia / Q000473:pathology; D000818:Animals; D017638:Asbestos, Crocidolite / Q000737:chemistry / Q000633:toxicity; D001201:Ascites / Q000175:diagnosis / Q000473:pathology; D001344:Autopsy / Q000379:methods; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000473:pathology; D006099:Granuloma / Q000139:chemically induced / Q000473:pathology; D007267:Injections; D008099:Liver / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced* / Q000473:pathology; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D010537:Peritoneum / Q000473:pathology; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D012611:Scrotum; D013535:Suspensions / Q000737:chemistry; D013997:Time Factors; D000267:Tissue Adhesions
D002273:Carcinogens; D037742:Nanotubes, Carbon; D014677:Pharmaceutical Vehicles; D013535:Suspensions; D017638:Asbestos, Crocidolite; D002266:Carboxymethylcellulose Sodium