82
cases, of the comparison of the effects of nanomaterials and of the chemical species
entering the system after their dissolution. Again, it is important that all studies
concerning the reproductive safety/toxicity of nanomaterials should include variables appropriate to rate the toxicity. Among these variable, we recall at least the
IC50 (or ID50), and the LC50, that are the concentrations lethal for the 50% of the
observed biological system, or inhibiting the same percentage of growth in cultured
cells. IC50 refers to concentration, ID50 to dose.
To conclude, the alternative methods in vitro are essential for the assessment of
the reproductive toxicity of nanomaterials, being predictive and efficiently reducing
the burden of traditional investigation of the reproductive safety, under the point of
view of the R3 concept, that is, reduction, refinement, and replacement of the
necessary tests in mammals.
References
Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol
Appl Pharmacol 233(3):404–410. https://doi.org/10.1016/j.taap.2008.09.015
Ahn RW, Barrett SL, Raja MR, Jozefik JK, Spaho L, Chen H, Bally MB, Mazar AP, Avram MJ,
Winter JN, Gordon LI, Shea LD, O’Halloran TV, Woodruff TK (2013) Nano-encapsulation
of arsenic trioxide enhances efficacy against murine lymphoma model while minimizing its
impact on ovarian reserve in vitro and in vivo. PLoS One 8(3):e58491. https://doi.org/10.1371/
journal.pone.0058491
Åkerlund E, Cappellini F, Di Bucchianico S, Islam S, Skoglund S, Derr R, Odnevall Wallinder I,
Hendriks G, Karlsson HL (2018) Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, γ-H2AX staining, Hprt mutation assay and ToxTracker
reporter cell lines. Environ Mol Mutagen 59(3):211–222. https://doi.org/10.1002/em.2216399
Akhavan O, Hashemi E, Zare H, Shamsara M, Taghavinia N, Heidari F (2016) Influence of heavy
nanocrystals on spermatozoa and fertility of mammals. Mater Sci Eng C Mater Biol Appl
69:52–59. https://doi.org/10.1016/j.msec.2016.06.055
Albekairi NA, Al-Enazy S, Ali S, Rytting E (2015) Transport of digoxin-loaded polymeric
nanoparticles across BeWo cells, an in vitro model of human placental trophoblast. Ther Deliv
6(12):1325–1334. https://doi.org/10.4155/tde.15.79
Ali H, Kalashnikova I, White MA, Sherman M, Rytting E (2013) Preparation, characterization,
and transport of dexamethasone-loaded polymeric nanoparticles across a human placental
in vitro model. Int J Pharm 454(1):149–157. https://doi.org/10.1016/j.ijpharm.2013.07.010
Arashiro EKN, Palhao MP, Wohlres-Viana S, Siqueira LGB, Camargo LSA, Henry M, Viana JHM
(2013) In vivo collection of follicular fluid and granulosa cells from individual follicles of different diameters in cattle by an adapted ovum pick-up system. Reprod Biol Endocrinol 11(73).
https://doi.org/10.1186/1477- 7827- 11- 73
Ariu F, Bogliolo L, Pinna A, Malfatti L, Innocenzi P, Falchi L, Bebbere D, Ledda S (2017)
Cerium oxide nanoparticles (CeO(2) NPs) improve the developmental competence of
in vitro-matured prepubertal ovine oocytes. Reprod Fertil Dev 29(5):1046–1056. https://doi.
org/10.1071/RD15521
Asghar W, Shafiee H, Velasco V, Sah VR, Guo S, El Assal R, Inci F, Rajagopalan A, Jahangir
M, Anchan RM, Mutter GL, Ozkan M, Ozkan CS, Demirci U (2016) Toxicology study of
single walled carbon nanotubes and reduced graphene oxide in human sperm. Sci Rep 6:30270.
https://doi.org/10.1038/srep30270
A. G. Cattaneo
cases, of the comparison of the effects of nanomaterials and of the chemical species
entering the system after their dissolution. Again, it is important that all studies
concerning the reproductive safety/toxicity of nanomaterials should include variables appropriate to rate the toxicity. Among these variable, we recall at least the
IC50 (or ID50), and the LC50, that are the concentrations lethal for the 50% of the
observed biological system, or inhibiting the same percentage of growth in cultured
cells. IC50 refers to concentration, ID50 to dose.
To conclude, the alternative methods in vitro are essential for the assessment of
the reproductive toxicity of nanomaterials, being predictive and efficiently reducing
the burden of traditional investigation of the reproductive safety, under the point of
view of the R3 concept, that is, reduction, refinement, and replacement of the
necessary tests in mammals.
References
Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol
Appl Pharmacol 233(3):404–410. https://doi.org/10.1016/j.taap.2008.09.015
Ahn RW, Barrett SL, Raja MR, Jozefik JK, Spaho L, Chen H, Bally MB, Mazar AP, Avram MJ,
Winter JN, Gordon LI, Shea LD, O’Halloran TV, Woodruff TK (2013) Nano-encapsulation
of arsenic trioxide enhances efficacy against murine lymphoma model while minimizing its
impact on ovarian reserve in vitro and in vivo. PLoS One 8(3):e58491. https://doi.org/10.1371/
journal.pone.0058491
Åkerlund E, Cappellini F, Di Bucchianico S, Islam S, Skoglund S, Derr R, Odnevall Wallinder I,
Hendriks G, Karlsson HL (2018) Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, γ-H2AX staining, Hprt mutation assay and ToxTracker
reporter cell lines. Environ Mol Mutagen 59(3):211–222. https://doi.org/10.1002/em.2216399
Akhavan O, Hashemi E, Zare H, Shamsara M, Taghavinia N, Heidari F (2016) Influence of heavy
nanocrystals on spermatozoa and fertility of mammals. Mater Sci Eng C Mater Biol Appl
69:52–59. https://doi.org/10.1016/j.msec.2016.06.055
Albekairi NA, Al-Enazy S, Ali S, Rytting E (2015) Transport of digoxin-loaded polymeric
nanoparticles across BeWo cells, an in vitro model of human placental trophoblast. Ther Deliv
6(12):1325–1334. https://doi.org/10.4155/tde.15.79
Ali H, Kalashnikova I, White MA, Sherman M, Rytting E (2013) Preparation, characterization,
and transport of dexamethasone-loaded polymeric nanoparticles across a human placental
in vitro model. Int J Pharm 454(1):149–157. https://doi.org/10.1016/j.ijpharm.2013.07.010
Arashiro EKN, Palhao MP, Wohlres-Viana S, Siqueira LGB, Camargo LSA, Henry M, Viana JHM
(2013) In vivo collection of follicular fluid and granulosa cells from individual follicles of different diameters in cattle by an adapted ovum pick-up system. Reprod Biol Endocrinol 11(73).
https://doi.org/10.1186/1477- 7827- 11- 73
Ariu F, Bogliolo L, Pinna A, Malfatti L, Innocenzi P, Falchi L, Bebbere D, Ledda S (2017)
Cerium oxide nanoparticles (CeO(2) NPs) improve the developmental competence of
in vitro-matured prepubertal ovine oocytes. Reprod Fertil Dev 29(5):1046–1056. https://doi.
org/10.1071/RD15521
Asghar W, Shafiee H, Velasco V, Sah VR, Guo S, El Assal R, Inci F, Rajagopalan A, Jahangir
M, Anchan RM, Mutter GL, Ozkan M, Ozkan CS, Demirci U (2016) Toxicology study of
single walled carbon nanotubes and reduced graphene oxide in human sperm. Sci Rep 6:30270.
https://doi.org/10.1038/srep30270
A. G. Cattaneo