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 Ca²⁺ 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.

• Nanocalcium carbonate
• physicochemical characteristics
• 90-day oral toxicity testing

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This research was supported by Ministry of Food and Drug Safety (13182MFDSS609, 13182MFDS606) and the Nano R&D Program, through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (2009-082712). M.H. Cho was also partially supported by the Research Institute for Veterinary Science, Seoul National University.

Supplementary material available online.

Supplementary Data Table S1–S16