title: Physico-chemical characterization-based safety evaluation of nanocalcium.
abstract: Nano- and microcalcium provided from the KFDA were compared in terms of physico-chemical properties. Calcium samples were tested using EF-TEM and X-ray diffractometry to check for size/morphology and crystal formation, respectively. Two samples of nano- and microcalcium were selected for further evaluation by FE-SEM, DLS (nano-size, 200-500nm; agglomerate, >5 μm; micro-size, 1.5-30 μm), and electron spin resonance. Both samples were heterogeneous in size, existed as single crystal and aggregated form, and did not generate reactive oxygen species. The specific surface area of nano- and microcalcium measured by N2 Brunauere Emmette Teller method was 12.90±0.27 m(2)/g and 1.12±0.19 m(2)/g, respectively. Inductively coupled plasma optical emission spectrometry analysis revealed the release of 2-3 times more calcium ion from nano- compared to microcalcium at pH 5 and 7. Genotoxicity and acute single-dose and repeated-dose 14-day oral toxicity testing in SD rats performed to evaluate the safety of nanocalcium did not reveal toxicity. However, long-term monitoring will be required for an unequivocal conclusion. A nanocalcium dose of 1 g/kg is recommended as the maximum dose for repeated dose 13-week oral toxicity. Further studies could provide details of toxicity of nanocalcium on the repeated dose 13-week oral toxicity test.
authors: R&D Center, Biterials, Gyeonggi-do 814-9, Republic of Korea.
authors: Min Sook
authors: MS
authors: Jeong
authors: Hyun Sun
authors: HS
authors: Cho
authors: Soo Jin
authors: SJ
authors: Park
authors: Kyung Seuk
authors: KS
authors: Song
authors: Kyu Sup
authors: KS
authors: Ahn
authors: Myung-Haing
authors: MH
authors: Cho
authors: Jun Sung
authors: JS
authors: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002118:Calcium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D003412:Cricetulus; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission / Q000379:methods; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests / Q000379:methods*; D023382:Toxicity Tests, Acute / Q000379:methods; D014961:X-Ray Diffraction
chemical_list: D002118:Calcium
keywords: Genotoxicity; Nanocalcium; Physico-chemical characteristics; Specific surface area