Abstract: Objective:To observe the toxic effects of cockle shell-derived calcium carbonate nanoparticles (CCNPs) on the SD rats, and to preliminarily explore the safe dose and biological effects of CCNPs. Methods:A total of 40 healthy male SD rats were randomly divided into control group, low, middle and high doses of CCNPs groups (given 0, 30, 60, and 120 mg·kg^-1 CCNPs). The injection was consecutively given through the lateral tail vein once per day for 14 d. The body weights and daily feed intakes of the rats in various groups were measured. The haematology indexes, serum biochemical indexes, relative weights of organs and histopathology of main organs of the rats in various groups were detected. Results:In the 14-day repeated dose toxicity experiment, two rats died in high dose of CCNPs group, while no rats died in low and middle doses of CCNPs groups. The body weights and daily average intakes of the rats in different doses of CCNPs groups were slightly lower than those in control group, but the differences were not statistically significant (P>0.05). There were no significant differences in the serum indexes of the rats between different doses of CCNPs groups and control group(P>0.05). Compared with control group, the relative weights of lung of the rats in different doses of CCNPs groups were increased significant (P<0.05); the relative weights of spleen of the rats in low and middle doses of CCNPs groups were increased significantly (P<0.05); while the relative weight of spleen of the rats in high dose of CCNPs group had no significant difference(P>0.05). The histopathological analysis results showed that the mild inflammatory infiltration was found in some organs of the rats in low dose of CCNPs group, while no obviously pathological changes were found. The obviously histopathological changes were observed in the main organs of the rats in middle and high doses of CCNPs groups, including inflammatory cell infiltration, slight disorder of hepatocytes arrangement, increased vacuoles in hepatocytes; thickening of alveolar interstitium and formation of granulomas in the lung tissue; swelling, rupture and even necrosis of cardiac muscle fibers; atrophy and fissures of glomerulus and so on. Conclusion:Intravenous administration of low dose of CCNPs couldn't cause sever acute toxicity reaction.

Key words: calcium carbonate, nanoparticles, drug delivery system, toxicity study, cockle shell