title: Physicochemical analysis and repeated-dose 90-days oral toxicity study of nanocalcium carbonate in Sprague-Dawley rats.
abstract: In our previous studies of nanocalcium carbonate, in which we performed physicochemical analysis, genotoxicity, acute single-dose and repeated-dose 14-day oral toxicity testings in Sprague-Dawley (SD) rats, nanocalcium carbonate did not show a difference in toxicity compared to vehicle control. Here, we provide the first report of a repeated-dose 90-day oral toxicity test of nanocalcium carbonate in Sprague-Dawley rats, with physicochemical comparison of micro and nanocalcium carbonate. We find that the two particles differ in size, hydrodynamic size, and specific surface area, with no differences in components, crystalline structure and radical production. In terms of ionization ability, nanocalcium carbonate was slightly more ionized within 1% than microcalcium carbonate at pH 5 and pH 7. In the repeated-dose 90-day oral toxicity test of nanocalcium carbonate, there was no significant toxicity, and similar blood concentrations of Ca(2+) compared to the vehicle control group. Based on our results, although nanocalcium carbonate has different physicochemical properties, nanocalcium carbonate does not differ from microcalcium carbonate in terms of toxicity. Based on the results, we suggest that the no-observed-adverse-effect level (NOAEL) of nanocalcium carbonate is 1000 mg kg(-1) day(-1) in SD rats according to the maximum dose (OECD guideline 408). However, the NOAEL might be higher than 1000 mg kg(-1) day(-1) because there were no adverse effects revealed by consistent pathological findings or biochemical parameter changes. To justify a safe concentration of nanocalcium carbonate, which is a low toxicity chemical, more data is required on dose levels above 1000 mg kg(-1). Our findings may be useful for creating safety guidelines for the use nanocalcium carbonate.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University , Seoul , Republic of Korea .
authors.forename: Jae Hyuck
authors.initials: JH
authors.lastname: Sung
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Min Sook
authors.initials: MS
authors.lastname: Jeong
authors.forename: Kyung Seuk
authors.initials: KS
authors.lastname: Song
authors.forename: Kyu Sup
authors.initials: KS
authors.lastname: Ahn
authors.forename: Hyun Ryol
authors.initials: HR
authors.lastname: Ryu
authors.forename: Han
authors.initials: H
authors.lastname: Lee
authors.forename: Mi Ryoung
authors.initials: MR
authors.lastname: Song
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002119:Calcium Carbonate / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D059550:Toxicity Tests, Subchronic
chemical_list: D002119:Calcium Carbonate
keywords: 90-day oral toxicity testing; Nanocalcium carbonate; physicochemical characteristics