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. 2023 Jan 5;20:1. doi: 10.1186/s12989-022-00511-9

Table 1.

Database summary of the analysis of 4 studies out of 48 selected studies

Ag NP
p-chem
Experimental model and mode of exposure Exposure dose, sampling time Biological/toxicological
Endpoints
Actual measurements and methods Result Potential key event(s) (KE nr. from AOP-Wiki)a Potential adverse outcomes (AOs) associated with the key event (AO nr. from AOP-Wikia References

Size: 50 nm

Shape: Spherical

Hydrodynamic size:113.4 ± 12.1 nm

Zeta potential: − 12.30 ± 0.4 mV

Adult male SD rats

Oral gavage

50 mg/kg bw, 3 months Sperm Evaluation Sperm Motility, Concentration, and Viability by eosin staining

Increased sperm morphological abnormalities

Decreased sperm concentrations motility

and viability

Decreased sperm quantity or quality in the adult, Decreased fertility (ID505, ID520)

Impaired fertility

(ID330, ID406)

[46]
Oxidative Status GSH level, CAT activity and lipid peroxidation MDA content in testicular tissue by commercial kits

Decreased CAT activity,

Increased MDA content,

Non-significant change in GSH level

Decreased protection against oxidative stress, Occurance oxidative stress (ID210, ID1112, ID1249, ID1538, ID1869)

Lipid Peroxidation (ID1445 or ID1511)

Oxidative Damage

(ID356)

Hormonal Assessment Serum testosterone, LH and FSH by ELISA kit Decreased testosterone, LH and FSH levels

Reduction, testosterone level (ID1613, ID1689, ID1612)

Reduced, Gonadotropins (ID1986)

Decreased sperm quantity or quality in the adult, Decreased fertility (ID505, ID520)
DNA damage DNA strand breaks in testicular tissue by COMET assay Increased DNA damage Increased DNA damage (ID1194) DNA Damage (ID1194)
Histopathological Examination Testis and Seminiferous tubules by Hematoxylin and Eosin (HE) staining

Testis and Seminiferous tubules

Histological alterations

Necrotic spermatogonial cells

Testicular atrophy

(ID1506)

Male reproductive tract malformations (ID348)

Reduced, Reproductive Success (ID675)

Size:45 nm

PVP (< 1%)

Zeta potential: − 20 mV

New Zealand White male rabbits

Intravenous

5 mM AgNP solution (0.6 mg/kg bw)

2 months (weekly)

Sperm Evaluation Sperm Volume, Concentration, and Viability Decreased sperm motility, concentration and volume Decreased sperm quantity or quality in the adult, Decreased fertility (ID505, ID520)

Impaired fertility

(ID330, ID406)

[88]
Oxidative Status MDA content, NO concentration, CAT and GPX Activity in sperm and blood samples by commercial kits

Increased NO, and MDA content

Decreased CAT activity, and GSH level

Decreased protection against oxidative stress, Occurence oxidative stress (ID210, ID1112, ID1249, ID1538, ID1869)

Lipid Peroxidation (ID1445 or ID1511)

Oxidative Damage

(ID356)

Size:40 nm

Shape: Spherical

Adult male NMRI mice

Oral gavage

500 mg/kg bw with a time interval of 24 h for 35 days Oxidative Status Total antioxidant capacity and Lipid peroxidation parameters Decrease in the total antioxidant capacity, Increased MDA content

Decreased protection against oxidative stress, Occurence oxidative stress (ID210, ID1112, ID1249, ID1538, ID1869)

Lipid Peroxidation (ID1445 or ID1511)

Oxidative Damage

(ID356)

[98]
Hormonal Assessment Serum testosterone level by comercial kits Decreased testosterone hormone Reduction, testosterone level (ID1613, ID1689, ID1612) Decreased sperm quantity or quality in the adult, Decreased fertility (ID505, ID520)
Histological parameters Testis, volume of interstitial tissue and seminiferous tubules Decreased mean volume of testicular tissue and volume of seminiferous tubules Decreased sperm density, mean number of spermatocytes, mean number of Sertoli cells Testicular atrophy (ID1506)

Male reproductive tract malformations (ID348)

Reduced, Reproductive Success (ID675)

Size:100 nm

Shape: Spherical SSA: 7.5329m2/g

Zeta potential: − 18.9 mV

Male Rats

Sub dermal

10 and 50 mg/kg bw, 7 and 28 days Sperm Evaluation Sperm motility, velocity by HE staining Decreased sperm motility and velocity Decreased sperm quantity or quality in the adult, Decreased fertility (ID505, ID520) Impaired fertility [47]
Oxidative Status MDA, GSH, CAT Increased Lipid peroxidization, Decreased SOD, CAT, GSH and total thiols Decreased protection against oxidative stress, Occurence oxidative stress (ID210, ID1112, ID1249, ID1538, ID1869)

Oxidative Damage

(ID356)

Hormonal Assessment Testosterone, LH and FSH Decreased testosterone, LH and FSH levels (dose dependent

Reduction, testosterone level (ID1613, ID1689, ID1612)

Reduced, Gonadotropins (ID1986)

Decreased sperm quantity or quality in the adult, Decreased fertility (ID505, ID520)
Histological parameters Cellular achitecture of testes and epididymis Degenerative alterations in the cellular architecture of testes and epididymis Testicular atrophy (ID1506)

Male reproductive tract malformations (ID348)

Reduced, Reproductive Success (ID675)

aAs several KEs and AOs are related to some of these cellular mechanisms, we indicate the title of only some of them, but the IDs of all of them are cited