Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats
Source abstract
Abstract
Calcium carbonate nanoparticles have shown promising potentials in the delivery of drugs and metabolites. There is however, a paucity of information on the safety of their intentional or accidental over exposures to biological systems and general health safety. To this end, this study aims at documenting information on the safety of subcutaneous doses of biogenic nanocrystals of aragonite polymorph of calcium carbonate derived from cockle shells (ANC) in Sprague-Dawley (SD) rats. ANC was synthesized using the top-down method, characterized using the transmission electron microscopy and field emission scanning electron microscope and its acute and repeated dose 28-day trial toxicities were evaluated in SD rats. The results showed that the homogenous 30 ± 5 nm-sized spherical pure aragonite nanocrystals were not associated with mortality in the rats. Severe clinical signs and gross and histopathological lesions, indicating organ toxicities, were recorded in the acute toxicity (29,500 mg/m 2 ) group and the high dose (5900 mg/m 2 ) group of the repeated dose 28-day trial. However, the medium- (590 mg/m 2 body weight) and low (59 mg/m 2 )-dose groups showed moderate to mild lesions. The relatively mild lesions observed in the low toxicity dosage group marked the safety margin of ANC in SD rats. It was concluded from this study that the toxicity of CaCO 3 was dependent on the particulate size (30 ± 5 nm) and concentration and the route of administration used.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Calcium Carbonate Crystallization and Inhibition · Microplastics and Plastic Pollution · Nanoparticles: synthesis and applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (59)
Show source-provided references
1. Aguilar F, Dusemund B, Galtier P, Gilbert J, Gott DM, Grilli S, Gürtler R, König J, Lambré C, Larsen J-C, Leblanc J-C, Mortensen A, Parent-Massin D, Pratt I, Rietjens IMCM, Stankovic I, Tobback P, Verguieva T, Woutersen RA (2011) Scientific opinion on re-evaluation of calcium carbonate (E 170) as a food additive. European Food Safety Authority (EFSA) Journal 9(7):231854 http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/2318.pdf
2. Awang-Hazmi AJ, Zuki ABZ, Noordin MM, Jalila A, Norimah Y (2007) Mineral composition of the cockle (Anadara granosa) shells of west coast of peninsular Malaysia and it’s potential as biomaterial for use in bone repair. J Anim Vet Adv 6(5):591–597 http://medwelljournals.com/abstract/?doi=javaa.2007.591.594
3. Borm PJ, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, Kreyling W, Lademann J, Krutmann J, Warheit D, Oberdorster E (2006) The potential risks of nanomaterials: a review carried out for ECETOC. Part Fibre Toxicol 3(11):1–35. doi: 10.1186/1743-8977-3-11 http://www.particleandfibretoxicology.com/content/3/1/1110.1186/1743-8977-3-11 ↗
4. CCA (Calcium Carbonate Association) (2005) Skin & eye irritation studies performed on calcium carbonate, Summary report, December 2005, Calcium Carbonate Association–Europe A.I.S.B.L. Member of IMA-Europe, p 1–2. http://www.cca-europe.eu/fileadmin/cca/CCA_new/CCA_Summary_report__final_.pdf
5. Colfen H, Mann S (2003) Review: higher-order organization by mesoscale self-assembly and transformation of hybrid nanostructures. Angew Chem Int Ed 42(21):2319–243110.1002/anie.200200562 ↗
6. Colvin VL (2003) The potential environmental impact of engineered nanomaterials. Nat Biotechnol 21:1166–117010.1038/nbt875 ↗
7. Combes C, Miao B, Bareille R, Rey C (2006) Preparation, physical-chemical characterisation and cytocompatibility of calcium carbonate cements. Biomaterials 27:1945–194510.1016/j.biomaterials.2005.09.026 ↗
8. Drobne D (2007) Nanotoxicology for safe nanotechnology. Arh Hig Rada Toksikol 58:471–478. doi: 10.2478/v10004-007-0040-410.2478/v10004-007-0040-4 ↗
9. Elsaesser A, Howard CV (2012) Toxicology of nanoparticles. Adv Drug Deliv Rev 64:129–13710.1016/j.addr.2011.09.001 ↗
10. Epple M (2003) Book review: biomineralization principles and concepts in bioinorganic materials chemistry. By Stephen Mann. Angew Chem Int Ed 42:381–382. doi: 10.1002/anie.20039014310.1002/anie.200390143 ↗
11. Garnett MC, Kallinteri P (2006) Nanomedicines and nanotoxicology: some physiological principles. Occup Med (Lond) 56:307–31110.1093/occmed/kql052 ↗
12. Greulich C, Diendorf J, Simon T, Eggeler G, Epple M, Koller M (2011) Uptake and intracellular distribution of silver nanoparticles in human mesenchymal stem cells. Acta Biomater 7:347–35410.1016/j.actbio.2010.08.003 ↗
13. Guo F, Li Y, Xu H, Zhao G, He X (2007) Size-controllable synthesis of calcium carbonate nanoparticles using aqueous foam films as templates. Mater Lett 61(27):4937–493910.1016/j.matlet.2007.03.075 ↗
14. Gwinn MR, Vallyathan V (2006) Nanoparticles: health effects prospects and constraints. Environ Health Perspectives 114:1818–182510.1289/ehp.8871 ↗
15. Harlan Laboratories (2010) Calcium carbonate (nano): oral gavage combined repeat dose toxicity study with reproduction/developmental toxicity screening test in the rat. Project number: 2974/0010. Unpublished study report provided by CCA-Europe. May 2011
16. He XW, Liu T, Chen YX, Cheng DJ, Li XR, Xiao Y et al (2008) Calcium carbonate nanoparticle delivering vascular endothelial growth factor-C siRNA effectively inhibits lymphangiogenesis and growth of gastric cancer in vivo. Cancer Gene Ther 15(3):193–202. doi: 10.1038/sj.cgt.770112210.1038/sj.cgt.7701122 ↗
17. Heaney RP (2002) Ethnicity, bone status, and calcium requirement. Nutr Res 22(1–2):153–178. doi: 10.1016/S0271-5317(01)00358-X10.1016/S0271-5317(01)00358-X ↗
18. Higaki M, Kameyama M, Udagawa M, Ueno Y, Yamaguchi Y, Igarashi R, Ishihara T, Mizushima Y (2006) Transdermal delivery of calcium carbonate-nanoparticles containing insulin. Diabetes Technology and Therapeutics 8(3):369–374. doi: 10.1089/dia.2006.8.369-37410.1089/dia.2006.8.369-374 ↗
19. Hodgson E (2010) A textbook of modern toxicology, 4th edn. Wiley, Hoboken ISBN 978-0-470-46206-5 (cloth)
20. Hoque ME, Shehryar M, Islam KMN (2013) Processing and characterization of cockle shell calcium carbonate (CaCO3) bioceramic for potential application in bone tissue Engineering. Journal of Material Science and Engineering 2(4):100013210.4172/2169-0022.1000132 ↗
21. Hristozov D, Malsch I (2009) Hazards and risks of engineered nanoparticles for the environment and human health. Sustainability 1:1161–1194. doi: 10.3390/su104116110.3390/su1041161 ↗
22. Huang S, Chen JC, Hsu CW, Chang WH (2009) Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model. Nanotechnology 20(37):37510210.1088/0957-4484/20/37/375102 ↗
23. Islam KN, Bakar MZBA, Noordin MM, Hussein MZB, Rahman NSBA, Ali ME (2011) Characterisation of calcium carbonate and its polymorphs from cockle shells (Anadara granosa). Powder Technol 213(1):188–19110.1016/j.powtec.2011.07.031 ↗
24. Islam, KN, Zuki, ABZ Ali ME, Bin Hussein, MZ, Noordin, MM Loqman, MY Wahid, H, MA Hakim and Abd Hamid, SB (2012) Facile Synthesis of Calcium Carbonate Nanoparticles from Cockle Shells. Hindawi Publishing Corporation. Journal of Nanomaterials 2012:5. doi: 10.1155/2012/53401010.1155/2012/534010 ↗
25. ISO/TS (International Organisation for Standardization/Technica Specification) (2015) Nanotechnologies-vocabulary-part 2: nano -objects. ISO/TC 229, 1, 2015–06, 01.040.07, 07.030. © 2015 ISO
26. Jaji AZ, Bakar MZBA, Mahmud R, Loqman MY, Hezmee MNM, Isa T, Wenliang F, Hammadi NI (2017) Synthesis, characterization, and cytocompatibility of potential cockle shell aragonite nanocrystals for osteoporosis therapy and hormonal delivery. Nanotechnol Sci Appl 10:23–3310.2147/NSA.S113030 ↗
27. Ji ZQ, Sun H, Wang H, Xie Q, Liu Y, Wang Z (2006) Biodistribution and tumor uptake of C60(OH) x in mice. J Nanopart Res 8:53–6310.1007/s11051-005-9001-5 ↗
28. Karlsson HL, Gustafsson J, Cronholm P, Möller L (2009) Size-dependent toxicity of metal oxide particles—a comparison between nano- and micrometer size. Toxicol Lett 188(2):112–118. doi: 10.1016/j.toxlet.2009.03.01410.1016/j.toxlet.2009.03.014 ↗
29. Khabbazi M, Harsij M, Hedayati AK, Gholipoor H, Gerami MH, Ghafari FH (2015) Effect of CuO nanoparticles on some hematological indices of rainbow trout Oncorhynchus mykiss and their potential toxicity. Nanomed J 2(1):67–73. doi: 10.7508/nmj.2015.01.00810.7508/nmj.2015.01.008 ↗
30. Kitano H (2002) Computational systems biology. Nature 420:206–210. doi: 10.1038/nature0125410.1038/nature01254 ↗
31. Kroll A, Pillukat MH, Hahn D, Schnekenburger J (2012) Interference of engineered nanoparticles with in vitro toxicity assays. Arch Toxicol 86:1123–1136. doi: 10.1007/s00204-012-0837-z10.1007/s00204-012-0837-z ↗
32. Loy JE, Guo JH, Severtson SJ (2004) Role of adsorption fractionation in determining the calcium carbonate scale inhibition performance of polydisperse sodium polyacrylate. Ind Eng Chem Res 43:1882–188710.1021/ie034078a ↗
33. Lu J, Liong M, Li Z, Zink J, Tamanoi E (2010) Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 6(16):1794–1805. doi: 10.1002/smll.20100053810.1002/smll.201000538 ↗
34. Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF (2008) Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 38(5):1404–141310.1002/eji.200737984 ↗
35. McLeod MC, Gale WF, Roberts CB (2004) Metallic nanoparticle production utilizing a supercritical carbon dioxide flow process. Langmuir 20(17):7078–708210.1021/la0493262 ↗
36. McNeil SE (2011) Characterization of nanoparticles intended for drug delivery. Methods Mol Biol 697:269. Humana Press. ISBN 1607619083, 9781607619086 DOI 10.1007/978-1-60327-198-1_1 , © Springer Science+Business Media, LLC 201110.1007/978-1-60327-198-1_1 ↗
37. Moorthi C, Manavalan R, Kathiresan K (2011) Nanotherapeutics to overcome conventional cancer chemotherapy limitations. Journal of Pharm Pharmaceutical Sciences 14:67–7710.18433/J30C7D ↗
38. Morose G (2010) The 5 principles of “design for safer nanotechnology”. Journal of Clean Production 18:285–28910.1016/j.jclepro.2009.10.001 ↗
39. Muhammad SI, Ismail M, Mahmud R, Esmaile MF, Zuki ABZ (2013) Bone mass density estimation: Archimede’s principle versus automatic x-ray histogram and edge detection technique in ovariectomized rats treated with germinated brown rice bioactives. Clin Interv Aging 8:1421–1431. doi: 10.2147/CIA.S49704 ISSN 1176-9092; ESSN: 1178-199810.2147/CIA.S49704 ↗
40. Naka K, Huang SC, Chujo Y (2006) Formation of stable vaterite with poly(acrylic acid) by the delayed addition method. Langmuir 22:7760–776710.1021/la060874k ↗
41. Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311:622–62710.1126/science.1114397 ↗
42. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A, Kreyling W, Cox C (2002) Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. Journal of Toxicological Environment Health A 65:1531–154310.1080/00984100290071658 ↗
43. Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–83910.1289/ehp.7339 ↗
44. OECD (Organisation for Economic Co-operation and Development) (2010) OECD Stat, (data base). doi: 10.1787/data-00285-en . Accessed 15 Mar 201610.1787/data-00285-en ↗
45. SafePharma Laboratories, (2008). Calcium carbonate: acute oral toxicity in the rat-fixed dose method. SPL Project Number 1992/0009. Unpublished study report provided by CCA-Europe.April 2011.
46. Sayes, C.M. and Warheit, D.B. (2009). Characterization of nanomaterials for toxicity assessment, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1 (2009) 660–670.10.1002/wnan.58 ↗
47. Smith CJ, Shaw BJ, Handy RD (2007) Toxicity of single walled carbon nanotubes to rainbow trout, (Oncorhynchus mykiss): respiratory toxicity, organ pathologies, and other physiological effects. Aquat Toxicol 82:94–109. doi: 10.1016/j.aquatox.2007.02.00310.1016/j.aquatox.2007.02.003 ↗
48. Stern ST, McNeil SE (2008) Nanotechnology safety concerns revisited. Toxicol Sci 101:4–2110.1093/toxsci/kfm169 ↗
49. The Royal Society (2004) Nanoscience and nanotechnologies: opportunities and uncertainties. The Royal Society & the Royal Academy of Engineering. ISBN 0 85403 604 0. Available at http://www.nanotec.org.uk/finalReport.htm . Accessed 2 Feb 2016
50. Ueno Y, Futagawa H, Takagi Y, Ueno A, Mizushima Y (2004) Drug-incorporating calcium carbonate nanoparticles for a new delivery system. Journal of Controlled Release, 2005 103(1):93–9810.1016/j.jconrel.2004.11.015 ↗
51. Wang L, Sondi I, Matijevic’ E (1999) Preparation of uniform needle-like aragonite particles by homogeneous precipitation. Journal of Colloid Interface Sciience 218:54510.1006/jcis.1999.6463 ↗
52. Wang C, Zhao J, Zhao X, Bala H, Wang Z (2006) Synthesis of nanosized calcium carbonate (aragonite) via a polyacrylamide inducing process. Powder Technol 163(3):134–13810.1016/j.powtec.2005.12.019 ↗
53. Xie S, Wang F, Wang Y, Zhu L, Dong Z, Wang X, Li X, Zhou W (2011) Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles. Part Fibre Toxicol 8:33. doi: 10.1186/1743-8977-8-3310.1186/1743-8977-8-33 ↗
54. Xu AW, Antonietti M, Colfen H, Fang YP (2006) Uniform hexagonal plates of vaterite calcium carbonate mesocrystals formed by biomimetic mineralization. Adv Funct Mater 16:90310.1002/adfm.200500716 ↗
55. Yacobi NR, Malmstadt N, Fazlollahi F, DeMaio L, Marchelletta R, Hamm-Alvarez SF, Borok Z, Kim KJ, Crandall ED (2010) Mechanisms of alveolar epithelial translocation of a defined population of nanoparticles. Am J Respir Cell Mol Biol 42:604–61410.1165/rcmb.2009-0138OC ↗
56. Yu, J. Guo, H., Davis, S. A., and Mann, S. (2006). “Fabrication of hollow inorganic microspheres by chemically induced self-transformation,” Adv Funct Mater, vol. 16, no. 15, pp. 2035–2041, 2006.10.1002/adfm.200600552 ↗
57. Zhang JC, Zhang J, Feng X, Li W, Zhao Y, Han B (2008) Influence of surfactant on themorphologies of CaCO3 by carbonation route with compressed CO2. Colloid Surface A 324(1–3):167–17010.1016/j.colsurfa.2008.04.010 ↗
58. Zhang X, Sun M, Zheng A, Cao D, Bi Y, Sun J (2012) Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration. Eur J Pharm Sci 45(5):632–638. doi: 10.1016/j.ejps.2012.01.00210.1016/j.ejps.2012.01.002 ↗
59. Zhanga Q, Rena L, Sheng Y, Ji Y, Fu J (2010) Control of morphologies and polymorphs of calcium carbonate via multi-additives system. Mater Chem Phys 122:156–16310.1016/j.matchemphys.2010.02.053 ↗