Evaluation of carcinogenicity and chronic toxicity associated with orthopedic implants in mice.
The carcinogenicity and chronic toxicity of 316L stainless steel, nickel, Ti-6A1-4V, hydroxyapatite (HA)-coated Ti-6A1-4V, aluminum oxide containing yttrium oxide, and zirconium oxide containing yttrium oxide were evaluated by implanting solid rods of each material in the thigh muscle of C57BL/6N mice for 24 months. Nickel alloy showed high carcinogenic and toxic potencies, whereas other materials showed no evidence of them. Tumors retaining nickel alloys were malignant fibrous histiocytoma or fibrosarcoma. In some cases, lymphomata that seemed to develop spontaneously were found around the implants because lymphocytes were known to accumulate in chronic inflammatory lesions, and this phenomenon also might be applied to lymphoma.
Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
K
K
Takamura
K
K
Hayashi
N
N
Ishinishi
T
T
Yamada
Y
Y
Sugioka
D000497:Alloys; D000537:Aluminum Oxide / Q000009:adverse effects; D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D015197:Carcinogenicity Tests; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced*; D018219:Histiocytoma, Benign Fibrous / Q000139:chemically induced*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000009:adverse effects*; D019736:Prostheses and Implants; D013193:Stainless Steel / Q000009:adverse effects; D014025:Titanium / Q000009:adverse effects; D015040:Zirconium / Q000009:adverse effects
D000497:Alloys; D001672:Biocompatible Materials; D013193:Stainless Steel; C031462:titanium alloy (TiAl6V4); D009532:Nickel; D015040:Zirconium; D014025:Titanium; D000537:Aluminum Oxide; C028541:zirconium oxide