The Effects of Nanomaterials as Endocrine Disruptors
Abstract
:1. Introduction
2. Impact of Endocrine Disrupting NPs on Reproductive Health
2.1. Effects of NPs on the Male Reproductive System
2.2. Effects of NPs on the Female Reproductive System
2.3. Estrogenic Effects of NPs
3. Impact of Endocrine Disrupting NPs on Thyroid Function
4. Impact of Endocrine Disrupting NPs on Insulin Action and Metabolism
5. Impact of Endocrine Disrupting NPs on the Neuroendocrine System
6. Other Effects of Endocrine Disrupting NPs
7. Impact of Endocrine Disrupting NPs on Invertebrate Species
8. Discussion and Conclusions
Conflicts of Interest
Abbreviations
8-OHdG | 8-hydroxy-2-deoxyguanosine |
ACTH | AdrenoCorticoTropic Hormone |
ADP | Adenosine Diphosphate |
Ag-HC-NPs | Hydrocarbon-coated silver Nanoparticles |
Ag-NPs | Silver Nanoparticles |
Ag-PS-NPs | Polysaccharide-coated silver Nanoparticles |
Al-NPs | Aluminum Nanoparticles |
Al2O3-NPs | Aluminium Oxide Nanoparticles |
ATP | Adenosine Triphosphate |
Au-NPs | Gold Nanoparticles |
C60HyFn | hydrated C60 fullerene |
CB | Carbon Black |
CB-NPs | Carbon Black Nanoparticles |
CdS-QDs | Cadmium Sulfide Quantum Dots |
CdS/CdTe capped-QDs | Cadmium Sulfide/Cadmium Tellurium capped-Quantum Dots |
CdSe-core-QDs | Cadmium Selenium core Quantum Dots |
CdTe-QDs | Cadmium Tellurium Quantum Dots |
CdTe/ZnTe QDs | Cadmium Tellurium/Zinc Tellurium Quantum Dots |
CeO2-NPs | Cerium Oxide Nanoparticles |
Chg | Choriogenin |
CHO | Chinese Hamster Ovary cells |
CNTs | Carbon Nanotubes |
COX-2 | Cyclooxygenase-2 |
CrCl3-NPs | Chromium Chloride Nanoparticles |
Cr-NPs | Chromium Nanoparticles |
Cu-NPs | Copper nanoparticles |
DA | Dopamine |
DE-NPs | Diesel Exhaust Nanoparticles |
DOPAC | dihydroxyphenylacetic acid |
DSP | Daily Sperm Production |
EDCs | Endocrine Disrupting Chemicals |
EDPL | Endocrine Disruptor Priority List |
ER | Estrogenic Receptor |
ERK | extracellular signal-regulated kinase |
EuOH3-NPs | Europium Hydroxied Nanoparticles |
Eu2O3-NPs | Europium Oxide Nanoparticles |
Fe3O4-NPs | Magnetic Iron Oxide Nanoparticles |
FSH | Follicle Stimulating Hormone |
FT3 | free triiodothyronine |
FT4 | free thyroxine |
GH | Growth Hormone |
GnRH | Gonadotropin Releasing Hormone |
HMG-CoA | 3-hydroxy-3-methylglutaryl-coenzyme A |
HVA | HomoVanillic Acid |
IGF-I | Insulin-like Growth Factor I |
IR | Insulin Resistance |
LDL-R | Low Density Lipoprotein Receptor |
LH | Luteinizing Hormone |
MAPKs | Mitogen-Activated Protein Kinases |
MARCO | Macrophage Receptor with Collagenous structure |
MN | Micro Nuclei |
MnO-NPs | Manganese Oxide Nanoparticles |
MoO3-NPs | Molybdenum Trioxide Nanoparticles |
mPEG@Au-NP | ω-methoxy poly(ethylene glycol) capped gold-NPs |
MTT | 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl- 2H-tetrazolium bromide |
MWCNTs | Multi Walled Carbon Nanotubes |
NPs | NanoParticles |
NRDE-NPs | Nanoparticle-Rich Diesel Exhaust Nanoparticles |
nSP | amorphous nanosilica particles |
Ntera2, NT2 | human testicular embryonic carcinoma cell line |
P450 17α | Cytochrome P450 17α |
P450 17β-HSD | Cytochrome P450 17β-HydroxySteroid Dehydrogenase |
P450arom | Aromatase P450 |
P450scc | Cytochrome P450 side-chain cleavage |
PBR | Peripheral-type Benzodiazepine Receptor |
PEG | PolyEthilen-Glycol |
PEG-NH2@Au-NP | ω-aminoethyl poly(ethylene glycol) capped gold-NPs |
POP | Persistent Organic Pollutants |
QDs | Quantum Dots |
RLKI | Rana Larval Keratin Type I |
ROS | Reactive Oxygen Species |
SCE | Sister Chromatid Exchanges |
SiCNWs | Silicon Carbide Nanowires |
s-MWCNTs-PEG | synthesized functionalized MWCNTs with polyethylene glycol |
SR-B1 | Scavenger Receptor class B type 1 |
SSC | Spermatogonial Stem Cells |
StAR | Steroidogenic Acute Regulatory protein |
T2DM | Type 2 Diabetes Mellitus |
TH | Thyroid Hormone |
TiO2 | Titanium Dioxide |
TiO2-NPs | Titanium Dioxide nanoparticles |
TRβ | Thyroid hormone Receptor β |
TSH | Thyrotropic-Stimulating Hormone |
UV | Ultra Violet |
VTG | Vitellogenin |
ZnO-NPs | Zinc Oxide Nanoparticles |
ZnS | Zinc Sulfide |
ZnS-QDs | Zinc Sulfide Quantum Dots |
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Type of category | Category 1 | Category 2 | Category 3a | Category 3b | References |
Criteria of classification | At least one in vivo study providing clear evidence of endocrine disruption in an intact organism | Potential for endocrine disruption. In vitro data indicating potential for endocrine disruption in intact organisms. Also includes effects in vivo that may, or may not be endocrine disruption-mediated. | No scientific basis for inclusion in list. Endocrine disruption studies available but no indications of endocrine disruption effects. | Substances with no or insufficient data gathered | |
Number of chemical substances in each category | 194 | 125 | 23 | 86 | [15–18] |
Type of study | Type and physico-chemical properties of NPs | Experimental protocol | Cell line/laboratory animals | Results | References |
---|---|---|---|---|---|
Alterations and impairment of testicular structure | |||||
In vitro | TiO2-NPs (25–70 nm); CB-NPs (14 nm); DE-NPs | Treatment with 0–1000 μg/mL for 24 and 48 h | Mouse testis Leydig cell line TM3 |
| [30] |
In vitro | 75% rutile and 25% anatase TiO2-NPs (24.5 nm) | Treatment with 0.5–50 μg/mL for 4, 24 and 48 h | RTG-2 cells |
| [31] |
In vitro | CeO2-NPs (10 nm and 20–25 nm) | Treatment with 0–100 μg/mL for 24 and 72 h | RTG-2 cells, derived from rainbow trout (Oncorhynchus mykiss) gonadal tissue |
| [32] |
In vivo | NRDE-NPs—Average of mode diameter and number concentrations for low, middle and high doses were 22.48, 26.13 and 27.06 nm; 2.27 × 105, 5.11 × 105 and 1.36 × 106, respectively | Inhalation exposure to low (15.37), middle (36.35) and high (168.84) μg/m3 doses for 4, 8, or 12 weeks (5 h/day, 5 days/week) | Fischer F344 rats |
| [33] |
In vivo | NRDE-NPs—Average of mode diameter and number concentrations were 26.81 nm and 1.83 × 106, respectively | Inhalation exposure to 148.86 μg/m3 for 5 h daily for 19 gestational days | Pregnant Fischer F344 rats |
| [34] |
In vivo | TiO2-NPs (anatase form, particle size of 25–70 nm, surface area 20–25 m2/g) | Subcutaneous injections of 100 μL of 1mg/mL solution on 4 gestational days | Pregnant Slc:ICR mice |
| [35] |
In vivo | CB-NPs (14, 56 and 95 nm with a surface area of 300, 45 and 20 m2/g, respectively) | Intratracheal administration of 0.1 mg/kg body weight for 10 times every week | ICR mice |
| [36] |
In vivo | Carboxylate-functionalized (diameter of 20–30 nm, length 0.5–2.0 μm) and Amine-functionalized (diameter of 20–30 nm, length 0.5–2.0 μm) MWCNTs | Mice were randomly divided into 12 groups (15-day single dose, 15-day multi-dose, 60-day multi-dose, and 90-day multi-dose groups). Mice were given injections (5 mg/kg) via the tail vein once (single dose) or every 3 days for 5 times | BALB/c mice |
| [37] |
In vivo | CB-NPs (14 nm) | Intratracheal administration of 0.2 mg/kg body weight on days 7 and 14 of gestation | Pregnant ICR mice |
| [38] |
In vivo | mPEG@Au-NP and PEG-NH2@Au-NP (14 nm) | Intravenous injection of 45 and 225 mg/kg of mPEG@Au-NP and 45 mg/kg of PEG-NH2@ Au-NP at 48 h intervals for 5 days | ICR mice |
| [39] |
In vivo | Amorphous silica particles (nSP70, 70-nm diameter; nSP300, 300-nm diameter) | Intravenous injection of 0.4 and 0.8 mg of nSP70 | BALB/c mice |
| [40] |
Alterations and impairment of spermatogenesis | |||||
In vitro | Fullerenol | Treatment with fullerenol (1, 10 and 100 μmol) for 3 h. | Epididymal sperm samples collected from the fresh epididymis of adult goats |
| [41] |
In vitro | Silver (15 nm), molybdenum (30 nm), and aluminum (30 nm) | Treatment with 5, 10, 25, 50, and 100 μg/mL culture medium for 48 h | C18-4 spermatogonial stem cell line |
| [42] |
In vitro | Magnetic iron oxide NPs (Fe3O4-NPs) coated with poly(vinyl alcohol) | Treatment with 7.35 mM for 80 min and 4 h | Bovine sperm cells |
| [43] |
In vitro | Eu2O3-NPs (30 ± 10 nm); EuOH3-NPs conjugated with polyvinyl alcohol or polyvinyl piyrolidone (15.4 ± 3 nm and 9.3 ± 3 nm, respectively) | 1 mL of washed sperm cells was incubated for 24 h at 39 °C with 2.5 mg/mL of Eu2O3-NPs or of EuOH3-NPs | Bovine sperm cells |
| [44] |
In vitro | TiO2-NPs and ZnO-NPs (40–70 nm) | Treatment with 3.73–59.7 μg/mL of TiO2-NPs and 11.5–93.2 μg/mL of ZnO-NPs | Human spermatozoa |
| [45] |
In vitro | Au-NPs (9 nm) | Analyses were conducted on a mixture of 500 μL of Au-NPs (44 ppm) solution and semen | Human spermatozoa |
| [46] |
In vitro | Hydrocarbon-coated silver (Ag-HC) nanoparticles of 15, 25, and 80 nm diameters and Polysaccharide-coated silver (Ag-PS) nanoparticles of 10, 25–30, and 80 nm diameters | Treatment with 5, 10, 25, 50, and 100 μg/mL culture medium for 24 h | C18-4 spermatogonial stem cell line |
| [47] |
In vitro | Au-NPs (5–65 nm) | Treatment with 0.5–50 μM for 2 h | Bovine spermatozoa |
| [48] |
In vitro | Au-NPs (~2.5 nm in diameter) | Treatment with concentrations of 0.5 × 1015 or 1 × 1015 particles/mL for 20 and 40 min | Epididymal sperm samples collected from the epididymis of hybrid mice CBA × C57B1/6 |
| [49] |
In vitro | Ag-NPs (65 nm) | Aliquots of total semen were incubated at 37 °C for 60 min and 120 min at the concentration of 125, 250 and 500 μM | Semen samples obtained from 10 healthy donors |
| [50] |
In vitro | Ag-NPs (20 nm) and TiO2-NPs (21 nm) | Cells were exposed for 24, 48 and 72 h to 10, 50 and 100 μg/mL, equivalent to 7.8, 15.6 and 31 μg/cm2, respectively | Ntera2 (NT2, human testicular embryonic carcinoma cell line) and primary testicular cells from C57BL6 mice of wild type (WT) and 8- oxoguanine DNA glycosylase knock-out (KO, mOgg1−/−) genotype |
| [51] |
In vivo | TiO2-NPs | Intraperitoneal injection of 200 and 500 μg/kg every other day for five times | ICR mice |
| [52] |
In vivo | TiO2-NPs (anatase form, particle size of 25–70 nm, surface area 20–25 m2/g) | Subcutaneous injections of 100 μL of 1 mg/mL solution | Pregnant Slc: ICR mice |
| [35] |
In vivo | CB-NPs (14, 56 and 95 nm with a surface area of 300, 45 and 20 m2/g, respectively) | Intratracheal administration of 0.1 mg/kg body weight every week for 10 times | ICR mice |
| [36] |
In vivo | Carboxylate-functionalized (diameter of 20–30 nm, length 0.5–2.0 μm) and Amine-functionalized (diameter of 20–30 nm, length 0.5–2.0 μm) MWCNTs | Mice were randomly divided into 12 groups (15-day single dose, 15-day multi-dose, 60-day multi-dose, and 90-day multi-dose groups). Mice were given injections (5 mg/kg) via the tail vein once (single dose) or every 3 days for 5 times | BALB/c mice |
| [37] |
In vivo | CB-NPs (14 nm) | Intratracheal administration of 0.2 mg/kg body weight of CB-NPs on days 7 and 14 of gestation | Pregnant female ICR mice |
| [38] |
In vivo | C60 fullerene (3–36 nm) | Rats received distilled water containing aqueous solutions of C60HyFn at concentration of 4~μg/kg daily for 5 weeks | Healthy and streptozotocin-induced diabetic male Wistar albino rats |
| [53] |
In vivo | Dimercaptosuccinic acid coated Fe3O4-NPs (3–9 nm) | Intraperitoneal injection in a single dose of 50, 100, 200 and 300 mg/kg | Female pregnant Balb/C mice |
| [54] |
In vivo | TiO2-NPs (33.2 ± 16.7 nm) | Administration by oral gavage of 40, 200 and 1000 mg/kg with volume of suspension 10 mL/kg of mouse weight | Male CBAxB6 mice |
| [55] |
In vivo | Ag-NPs with a nominal diameter of 20 ± 5 nm | Intravenous injection with a single dose (5 mg/kg or 10 mg/kg) of Ag-NPs | Wistar rats |
| [56] |
In vivo | mPEG@Au-NP and PEG-NH2@Au-NP (14 nm) | Intravenous injection of 45 and 225 mg/kg of mPEG@Au-NP and 45 mg/kg of PEG-NH2@Au-NP at 48 h intervals for 5 days | ICR mice |
| [39] |
In vivo | Nude short MWCNTs (50–200 nm) and synthesized functionalized MWCNTs with polyethylene glycol (PEG) (s-MWCNTs-PEG). | Intravenous administration with a single dose of 100 μg/kg body weight | Kunming mice |
| [57] |
In vivo | Powder of nanoparticulate TiO2 (primary particle size was 20.6 nm, in the exposure atmosphere the particle number concentration was 1.7 × 106 particles/cm3 and the major particle size mode was 97 nm); nanosized CB (particle size was 14 nm) | Mice were exposed by whole body inhalation, 1 h/day from gestation day 8 to 18, to 42 mg/m3 of aerosolized powder of nanoparticulate TiO2; mice were intratracheally instilled four times during gestation, (days 7, 10, 15 and 18) with 67 μg/animal of nanosized CB | Pregnant female C57BL/6J mice |
| [58] |
Disruption of normal levels of sex hormones | |||||
In vitro | TiO2-NPs (25–70 nm); CB-NPs (14 nm); DE-NPs | Treatment with 0–1000 μg/mL for 24 and 48 h | Mouse testis Leydig cell line TM3 |
| [30] |
In vitro | NRDE-NPs | Mice were exposed to 152.01 μg/m3 of NRDE-NPs for 8 weeks | Interstitial testicular cells, dissected from male C57BL/Jcl mice |
| [59] |
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations for low, middle and high doses were 22.48, 26.13 and 27.06 nm; 2.27 × 105, 5.11 × 105 and 1.36 × 106, respectively | Inhalation exposure to low (15.37), middle (36.35) and high (168.84) μg/m3 doses for 4, 8, or 12 weeks (5 h/day, 5 days/week) | Fischer F344 rats |
| [33] |
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations were 26.81 nm and 1.83 × 106, respectively | Inhalation exposure to 148.86 μg/m3 for 5 h daily for 19 gestational days | Pregnant Fischer F344 rats and male offspring |
| [34] |
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations for low, middle and high doses were 22.48, 26.13 and 27.06 nm; 2.27 × 105, 5.11 × 105 and 1.36 × 106, respectively | Inhalation exposure to low (15.37), middle (36.35) and high (168.84) μg/m3 doses for 4, 8, or 12 weeks (5 h/day, 5 days/week) | Fischer F344 rats |
| [60] |
In vivo | CB-NPs (14, 56 and 95 nm with a surface area of 300, 45 and 20 m2/g, respectively) | Intratracheal administration of 0.1 mg/kg body weight for 10 times every week | ICR mice |
| [36] |
In vivo | Carboxylate-functionalized (diameter of 20–30 nm, length 0.5–2.0 μm) and Amine-functionalized (diameter of 20–30 nm, length 0.5–2.0 μm) MWCNTs | Mice were randomly divided into 12 groups (15-day single dose, 15-day multi-dose, 60-day multi-dose, and 90-day multi-dose groups). Mice were given injections (5 mg/kg) via the tail vein once (single dose) or every 3 days for 5 times | BALB/c mice |
| [37] |
In vivo | CB-NPs (14 nm) | Intratracheal administration of 200 μg of CB-NPs on days 7 and 14 of gestation | Pregnant female ICR mice |
| [38] |
In vivo | NRDE-NPs | Mice were exposed to 152.01 μg/m3 of NRDE-NPs for 8 weeks | C57BL/Jcl mice |
| [59] |
In vivo | mPEG@Au-NP and PEG-NH2@Au-NP (14 nm) | Intravenous injection of 45 and 225 mg/kg of mPEG@Au-NP and 45 mg/kg of PEG-NH2@ Au-NP at 48 h intervals for 5 days | ICR mice |
| [39] |
In vivo | NRDE-NPs | Inhalation exposure to low (38 ± 3 μg/m3) and high (149 ± 8 μg/m3) NRDE-NP concentrations | Fischer F344 rats |
| [61] |
Type of study | Type and physico-chemical properties of NPs | Experimental protocol | Cell line/laboratory animals | Results | References |
---|---|---|---|---|---|
Effects on ovarian cells | |||||
In vitro | Anatase TiO2-NPs (30 nm) | Treatment with increasing concentrations of TiO2-NPs (0–100 μg/mL) for 24 h | CHO-K1 |
| [68] |
In vitro | TiO2-NPs (anatase-80% rutile-20% with organic coating, ~21 nm; anatase-80% rutile-20% doped with di-iron trioxide, ~21 nm; anatase-80% rutile-20%, ~21 nm; rutile 100% with inorganic and organic coating, 14 nm; anatase 100% with inorganic coating, 60 nm; rutile 100% with inorganic and organic coating, 20 nm; rutile 100% with inorganic and organic coating, 15 nm; rutile 100% with inorganic coating, 20–22 nm) | Exposure for 3 h to different concentrations of TiO2-NPs (800, 1950, 3000, 5000 μg/mL) | CHO-WBL |
| [69] |
In vitro | TiO2-NPs (rutile-79% anatase-21%, particle size: 140 ± 44 nm, surface area: 38.5 m2/g) | Cytogenetic evaluations were conducted exposing cells to 750, 1250, and 2500 μg/mL for the 4 h non-activated test condition, to 62.5, 125, and 250 μg/mL, for the 4 h activated test condition, and to 25, 50, and 100 μg/mL for the 20 h non-activated test condition. | CHO |
| [70] |
In vitro | Anatase TiO2-NPs (10–20, 50–60 nm) and rutile TiO2-NPs (50–60 nm) | Treatment with increasing concentrations of TiO2-NPs (25–325 μg/mL) for 24 h | CHO |
| [71] |
In vitro | TiO2-NPs (shape: complex; average particle sizes: 20 ± 7 nm; specific surface area: 142 m2/g) and Al2O3-NPs (shape: spherical; average particle sizes: 28 ± 19 nm; specific surface area: 39 m2/g) | Treatment with increasing concentrations of NPs (0.5, 1, 5, 10, 25, 50 and 100 μg/mL) for 24 h | CHO-K1 |
| [72] |
In vitro | SiCNW (diameter of 80 nm; chemical composition: Si to C ratio close to 1:1) | Exposure to different concentrations (0.5, 1.0, 5.0 and 10.0 μg/mL) of SiCNWs for 1, 3, and 5 days | CHO |
| [73] |
In vitro | Calcium phosphate-NPs (20–30 nm, less than 10% particles were greater than 100 nm) | Cells were divided into different groups of exposure: control (treated with 4-androstene-3,17-dione), group II (treated with 10 μM of Calcium phosphate-NPs and 4-androstene-3, 17-dione) and group III (treated with 100 μM of Calcium phosphate-NPs and 4-androstene-3, 17-dione) | Granulosa cells collected from infertilite women |
| [74] |
In vitro | MWCNTs (diameter ~10 nm) | In order to observe if the MWNT sheets have any toxic effect on cells, CHO cells were allowed to grow on the substrates until about 90% confluence | CHO |
| [75] |
In vitro | Anatase TiO2-NPs (<25 nm) | Cells were maintained under exponential growth conditions and were continuously exposed for 1, 2, or 60 days to either 0, 10, 20, 40, 100 and 200 μg/mL of NPs | CHO-K1 |
| [76] |
In vitro | Anatase TiO2-NPs (<25 nm) | Treatment with different concentrations of NPs (0, 25, 50, 100 and 200 μg/mL). Cells were incubated for 24 h and 48 h. | CHO-K1 |
| [77] |
In vitro | Naked mesoporous silica NPs (10 nm and 50 nm); carboxyl or amine modified mesoporous silica NPs; carboxyl-modified polystyrene-NPs (30 nm); polystyrene-NPs functionalized with amine groups (50 nm) | Exposure of NIH-OVCAR3 for 48 h to 30 and 75 μg/mL of naked mesoporous silica NPs (10 nm); exposure of NIH-OVCAR3 and SKOV3 cells for 1 and 24 h to 20 μg/mL of naked mesoporous silica NPs (50 nm) and of carboxyl or amine modified mesoporous silica NPs; exposure of NIH-OVCAR3 and SKOV3 cells for 24 and 48 h to 75 μg/mL of carboxyl-modified polystyrene-NPs and polystyrene-NPs functionalized with amine groups | Ovarian NIHOVCAR3 epithelial cancer cells; SKOV3 cancer cells |
| [78] |
In vitro | MWCNTs (average diameter: 67 nm; surface area: 26 m2/g; carbon purity: 99.79 wt%) | Exposure for 24 h to 1, 10 and 100 μg/mL of NPs | MARCO-transfected CHO-K1 cells |
| [79] |
Effects on oogenesis and follicle maturation | |||||
In vitro | TiO2-NPs (25 nm) | Exposure to increasing concentrations (12.5–50 μg/mL) of TiO2-NPs | Rat preantral follicles |
| [80] |
In vitro | CdSe-core-QDs and ZnS-coated CdSe QDs (3.5 nm) | Exposure for 24 h to 0, 125, 250 and 500 nM of CdSe-core-QDs and to 500 nM of ZnS-coated CdSe QDs | Cumulus-oocyte complexes collected from female ICR mice |
| [81] |
In vitro | Lysine coated CdSe/CdS/ZnS QDs (~20 nm) | Exposure for 4, 8, 16 and 24 h to 5.78 nmol/L and 29.8 nmol/L of Lysine coated CdSe/CdS/ZnS QDs | Immature oocytes of 28 days Kunming mice |
| [82] |
In vitro | CdSe/CdS/ZnS QDs | Exposure for 4, 8 and 20 h to 28.9 nmol/L of QDs | Immature oocytes were collected from Kunming mice |
| [83] |
In vitro | CdTe/ZnTe QD-Transferrin bioconjugates | Preantral follicles were treated with escalating concentrations of (0.0289, 0.289, 2.89 and 28.9 nmol/L) CdTe/ZnTe QD-Transferrin bioconjugates for 8 days | Pre antral follicles were collected from female Kunming mice |
| [84] |
In vivo | TiO2-NPs (anatase; NPs were found to aggregate in culture medium and consequently the mean sizes were 240–280 nm (0.1 mg/L) and 259–360 nm (1.0 mg/L) | Reproductively active fish were exposed for 13 weeks to 0.1 and 1.0 mg/L | Zebrafish Danio rerio |
| [85] |
In vivo | TiO2-NPs (anatase, average particle size: 6 nm, surface area: 174.8 m2/g) | TiO2-NPs suspensions at different concentrations (2.5, 5, and 10 mg/kg of body weight) were administered to mice by intragastric administration for 90 consecutive days. | CD-1 (ICR) female mice |
| [86] |
In vivo | Ag-NPs (3 and 35 nm) | Exposure to 10 μg/L of Ag-NPs for 35 days | Sheepshead minnows (Cyprinodon Variegatus) |
| [87] |
In vivo | TiO2-NPs (anatase-75% rutile-25%, average primary particle size: 21 nm, specific surface area: 50 ± 15 m2/g) | Reproductively active fish were exposed for 14 days to 0.1 and 1.0 mg/L | Zebrafish Danio rerio |
| [88] |
Disruption of normal levels of sex hormones | |||||
In vitro | Au-NPs (10 nm) | Exposure for 1,3,5 and 24 h to 2.85 × 1010 NPs/mL | Rat granulosa cells |
| [89] |
In vitro | Calcium phosphate-NPs (20–30 nm, less than 10% particles were greater than 100 nm) | Cells were divided into different groups of exposure: control (treated with 4-androstene-3,17-dione), group II (treated with 10 μM of Calcium phosphate-NPs and 4-androstene-3, 17-dione) and group III (treated with 100 μM of Calcium phosphate-NPs and 4-androstene-3, 17-dione) for 48 h | Granulosa cells collected from infertile women |
| [74] |
In vitro | CdTe/ZnTe QD-Transferrin bioconjugates | Preantral follicles were treated with escalating concentrations of (0.0289, 0.289, 2.89 and 28.9 nmol/L) CdTe/ZnTe QD-Transferrin bioconjugates for 8 days | Pre antral follicles were collected from female Kunming mice |
| [84] |
In vivo | TiO2-NPs (anatase, average particle size: 6 nm, surface area: 174.8 m2/g) | TiO2-NP suspensions at different concentrations (2.5, 5, and 10 mg/kg of body weight) were administered to mice by intragastric administration for 90 consecutive days. | CD-1 (ICR) female mice |
| [86] |
In vivo | NRDE-NPs (22–27 nm; particle composition showed a higher percentage of organic carbon than elemental carbon) | Inhalation exposure, for 5 h daily from day 1 to 19 of gestation, to 148.86 μg/m3 | Pregnant Fischer 344 rats |
| [90] |
In vivo | ZnO-NPs (20–30 nm) | Oral administration of 333.33 mg/kg of ZnO-NPs | Wistar rats |
| [91] |
Type of study | Type and physico-chemical properties of NPs | Experimental protocol | Cell line/laboratory animals | Results | References |
---|---|---|---|---|---|
In vitro | CdTe-QDs (~3 nm) | Treatment with 0.5 and 10 μg/mL for time periods ranging from 5 min to 96 h | Human breast cancer MCF-7 cells |
| [99] |
In vivo | CdS-QDs (4.2 ± 1 nm) | Exposure for 21 days to 5, 50 and 500 μg/L of CdS-QDs | Male sticklebacks (Gasterosteus aculeatus) |
| [95] |
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations for low, middle and high doses were 22.48, 26.13 and 27.06 nm; 2.27 × 105, 5.11 × 105 and 1.36 × 106, respectively | Inhalation exposure to low (15.37), middle (36.35) and high (168.84) μg/m3 doses for 4, 8, or 12 weeks (5 hours/day, 5 days/week) | Fischer F344 rats |
| [33] |
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations were 26.81 nm and 1.83 × 106, respectively | Inhalation exposure to 148.86 μg/m3 for 5 h daily for 19 gestational days | Pregnant Fischer F344 rats |
| [34] |
In vivo | (CdS)/CdTe capped-QDs | Exposure for 48 h to increasing concentrations of (CdS)/CdTe capped-QDs (1, 2 and 6 μg/L) | Juvenile rainbow trout (Oncorhynchus mykiss) |
| [94] |
In vivo | C60 fullerene | Male zebrafish (Danio rerio) were fed for 5 days with brine shrimp preparations that had accumulated a mixture of C60 fullerene (10% v/v of the 600 mg C60/900 mL water) and 1 μg/L of 17α-ethinylestradiol or C60 fullerene or 17α-ethinylestradiol alone. | Male zebrafish (Danio rerio) |
| [97] |
In vivo | CB-NPs (50–60 nm) | Intratracheal instillation at a total dose of 11, 54 and 268 μg/animal during gestation (7, 10, 15 and 18 gestation days) | C57BL/6 mice |
| [100] |
In vivo | C60 fullerene | Exposure of male zebrafish (Danio rerio) to increasing concentrations of C60 fullerene. See Park et al. (2010) | Male zebrafish (Danio rerio) |
| [98] |
In vivo | Ag-NPs (20 nm) | Exposure to increasing concentrations of Ag-NPs (0.06, 0.6 and 6 μg/L) for 96 h | Juvenile rainbow trout (Oncorhynchus mykiss) |
| [93] |
In vivo | NRDE-NPs Low dose group (average of mode diameter: 22.78 ± 0.39 nm; mass concentration: 41.73 ± 0.58 μg/m3; number concentration: 8.21 × 105 ± 3.1 × 105), High dose group (average of mode diameter: 26.31 ± 0.38 nm; mass concentration: 152.01 ± 1.18 μg/m3; number concentration: 1.8 × 106 ± 5.18 × 105) | Exposure for 8 weeks (5 h/day, 5 days/week) to 41.73 μg/m3 and 152.01 μg/m3 of NRDE-NPs | Male C57BL/Jcl mice |
| [96] |
In vivo | Ag-NPs (23.5 ± 4.4 nm) | Exposure to 1 and 25 μg/L of Ag-NPs for 28 days | Male Medaka (Oryzias latipes) fish |
| [92] |
Type of study | Type and physico-chemical properties of NPs | Experimental protocol | Cell line/laboratory animals | Results | References |
---|---|---|---|---|---|
Effects on thyroid function | |||||
In vitro | Ag-NPs (2–6 and 10 nm), ZnO-NPs (2–10 and 9 nm) and QDs composed of cadmium telluride (2–10 and 10–15 nm) | Exposure of cultured tail fin biopsy to 0.06 μg/L–5.5 mg/L of Ag-NPs, 0.19–10 mg/L of ZnO-NPs and 0.25 μg/L–22 mg/L of QDs for 48 h | Cultured tail fin biopsy assay derived from Rana catesbeiana tadpoles |
| [105] |
In vivo | Cr-NPs (40–70 nm) | Oral administration of 150, 300 and 450 μg/Kg of Cr-NPs for 8 weeks | Male Sprague Dawley rats |
| [106] |
Effects on insulin action and metabolism | |||||
In vitro | TiO2-NPs (21 nm) | Exposure for 2 h to 50 and 200 μg/mL of TiO2-NPs | Fao rat hepatoma cells |
| [110] |
In vitro | CeO2-NPs (100 nm) | Exposure to 100 nmol/L of CeO2-NPs, alone or in combination with 30 nmol/L of sodium selenite for 1–6 days | Pancreatic islets |
| [111] |
In vivo | CrCl3-NPs (40–70 nm) | Dietary supplementation for 35 days with 200 μg/kg of CrCl3-NPs | Crossbred pigs (Duroc X Landrace X Yorkshire) |
| [112] |
In vivo | Cr-NPs (40–50 nm) | Oral administration for 6 weeks of 75, 150, 300, 450, 600 and 1200 ppb of Cr-NPs | Male Sprague Dawley rats |
| [113] |
In vivo | Cr-NPs (40–70 nm) | Oral administration of 150, 300 and 450 μg/Kg of Cr-NPs for 8 weeks | Male Sprague Dawley rats |
| [106] |
In vivo | Double walled-CNTs (0.5–2.5 nm for inner tubes and 1.2–3.2 nm for outer tubes) | Intranasal instillation of 1.5 mg/kg | Male Swiss mice |
| [114] |
In vivo | CeO2-NPs | Intraperitoneal injection of 60 mg/Kg of CeO2-NPs for 2 weeks, alone or in combination with sodium selenite (5 μmol/kg/day) | Male Wistar rats |
| [115] |
Effects on neuroendocrine system | |||||
In vitro | C60 fullerene | Exposure for 4 h to 100 μM of C60 fullerene | Adrenal chromaffin cells obtained from Wistar rats |
| [116] |
In vitro | MnO-NPs (40 nm) and Ag-NPs (15 nm) | Exposure for 24 h to increasing concentrations (1–100 μg/mL ) of NPs | PC-12 cells derived from Rattus norvegicus pheochromocytoma (CRL-1721) |
| [117] |
In vitro | Cu-NPs (90.9 ± 19.3 nm), Mn-NPs (52.1 ± 23.8 nm) and Ag-NPs (18.3 ± 7.3 nm) | Treatment for 24 h with 10 μg/mL of NPs and with increasing concentrations of Cu-NPs (2.5, 5, 7.5, 10 and 25 μg/mL) | PC-12 cells |
| [118] |
In vitro | Au-NPs (28 nm) and Ag-NPs (61 nm) | Treatment for 24 and 48 h with 0.01–1 nM of NPs | Primary culture murine adrenal medullary chormaffin cells harvested from wild-type brown male mice (C57BL/6J) |
| [119] |
In vitro | Carboxyl QDs with CdSe core and ZnS shell (7–8 nm) | Exposure for 24 h to increasing concentrations of QDs (5, 8, 16 and 36 nM) | Mouse chromaffin cells obtained from young C57BL/6J male mice |
| [120] |
In vitro | Ag-NPs coated with citrate (6 nm) or polyvinylpyrrolidone (21 nm) | Exposure for 24 h to different concentrations (1–30 μM) of Ag-NPs | PC-12 cells |
| [121] |
In vitro | Silica NPs (15 nm) | Exposure for 24 h to 25–200 μg/mL of silica NPs | PC-12 cells |
| [122] |
In vitro | Citrated-capped Ag-NPs (from 15 to 60 nm); PEG (25.6 ± 7.8 nm) and heparin (20.6 ± 15.3 nm) surface modified Au NPs. | Exposure for 24 h to citrated-capped Ag-NPs at 1 nM concentration and to PEG and heparin Au NPs at 10 μg/mL | Primary culture murine adrenal medullary chormaffin cells harvested from wild-type brown male mice (C57BL/6J) |
| [123] |
Effects on pituitary gland | |||||
In vivo | CrCl3-NPs (40–70 nm) | Dietary supplementation for 35 days with 200 μg/kg of CrCl3-NPs | Crossbred pigs (Duroc X Landrace X Yorkshire) |
| [112] |
In vivo | CrCl3-NPs (40–70 nm) | Dietary supplementation for 35 days with 200 μg/kg of CrCl3-NPs | Crossbred pigs (Duroc X Landrace X Yorkshire) |
| [124] |
In vivo | Cr-NPs (40–70 nm) | Oral administration of 150, 300 and 450 μg/Kg of Cr-NPs for 8 weeks | Male Sprague Dawley rats |
| [106] |
Effects on adrenal gland | |||||
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations for low, middle and high doses were 22.48, 26.13 and 27.06 nm; 2.27 × 105, 5.11 × 105 and 1.36 × 106, respectively | Inhalation exposure to low (15.37), middle (36.35) and high (168.84) μg/m3 doses for 4, 8, or 12 weeks (5 h/day, 5 days/week) | Fischer F344 rats |
| [33] |
In vivo | NRDE-NPs—Averages of mode diameter and number concentrations were 26.81 nm and 1.83 × 106, respectively | Inhalation exposure to 148.86 μg/m3for 5 h daily for 19 gestational days | Pregnant Fischer F344 rats |
| [34] |
In vivo | Cr-NPs (40–70 nm) | Oral administration of 150, 300 and 450 μg/Kg of Cr-NPs for 8 weeks | Male Sprague Dawley rats |
| [106] |
In vivo | NRDE-NPs Low dose group (average of mode diameter: 22.78 ± 0.39 nm; mass concentration: 41.73 ± 0.58 μg/m3; number concentration: 8.21 × 105 ± 3.1 × 105), High dose group (average of mode diameter: 26.31 ± 0.38 nm; mass concentration: 152.01 ± 1.18 μg/m3; number concentration: 1.8 × 106 ± 5.18 × 105) | Exposure for 8 weeks (5 h/day, 5 days/week) to 41.73 μg/m3 and 152.01 μg/m3 of NRDE-NPs | Male C57BL/Jcl mice |
| [96] |
In vivo | NRDE-NPs (22–27 nm; particle composition showed a higher percentage of organic carbon than elemental carbon) | Inhalation exposure to 148.86 μg/m3 for 5 h daily from day 1 to 19 of gestation | Pregnant Fischer 344 rats |
| [90] |
© 2013 by the authors; licensee MDPI, Basel, Switzerland This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Iavicoli, I.; Fontana, L.; Leso, V.; Bergamaschi, A. The Effects of Nanomaterials as Endocrine Disruptors. Int. J. Mol. Sci. 2013, 14, 16732-16801. https://doi.org/10.3390/ijms140816732
Iavicoli I, Fontana L, Leso V, Bergamaschi A. The Effects of Nanomaterials as Endocrine Disruptors. International Journal of Molecular Sciences. 2013; 14(8):16732-16801. https://doi.org/10.3390/ijms140816732
Chicago/Turabian StyleIavicoli, Ivo, Luca Fontana, Veruscka Leso, and Antonio Bergamaschi. 2013. "The Effects of Nanomaterials as Endocrine Disruptors" International Journal of Molecular Sciences 14, no. 8: 16732-16801. https://doi.org/10.3390/ijms140816732