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Table 1 Database summary of the analysis of 4 studies out of 48 selected studies

From: Putative adverse outcome pathways for silver nanoparticle toxicity on mammalian male reproductive system: a literature review

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)

  1. 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