Silver

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Substance considered to fall within the scope of the read-across 'Nanosilver: Justification of a read-across approach for human health hazard endpoints' (document attached in IUCLID section 13).

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: OECD443 Extended One Generation Reproductive Toxicity Study

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Route of administration:

oral: feed

Dose / conc.:

120 mg/kg bw/day (actual dose received)

Dose / conc.:

80 mg/kg bw/day (actual dose received)

Dose / conc.:

40 mg/kg bw/day (actual dose received)

Key result

Dose descriptor:

LOAEL

Effect level:

<= 40 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

gross pathology

Remarks on result:

other: degeneration in stomach mucosa in females at all doses - cfr. Renaut et al 2022 under section 'Reproductive toxicity'

Key result

Dose descriptor:

NOAEL

Effect level:

>= 120 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other:

Remarks on result:

other: cfr. Renaut et al 2022 under section 'Reproductive toxicity'

Key result

Dose descriptor:

NOAEL

Remarks:

F1 (cohort 2A)

Effect level:

ca. 40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: neuropathology

Remarks on result:

other: cfr. Renaut et al 2022 under section 'Reproductive toxicity'

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 80 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other:

Remarks on result:

other: cfr. Renaut et al 2022 under section 'Reproductive toxicity'

Key result

Developmental effects observed:

yes

Lowest effective dose / conc.:

40 mg/kg bw/day (nominal)

Treatment related:

yes

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

It was therefore concluded that the various no observed adverse effect levels (NOAELs) on this study were:

- F1 offspring survival and growth up to weaning: 80 mg/kg/day

- Developmental neurotoxicity in selected F1 animals: 40 mg/kg/day (due to the following effects of treatment at 80 or 120 mg/kg/day: reduced activity and rearing of males and females in the arena, reduced reactivity, abnormal motor movement/gait, intramyelinic edema and neuronal and/or glial cell necrosis and F1 brain morphometry (low mean hippocampus)

- Developmental immunotoxicity in selected F1 animals – 120 mg/kg/day (highest dose tested)

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Silver

EC Number:

231-131-3

EC Name:

Silver

Cas Number:

7440-22-4

Molecular formula:

Ag

IUPAC Name:

Silver

Test material form:

solid: nanoform, surface-treated

Remarks:

paste of nanomaterial

Details on test material:

Spherical particles
Particle size distribution (primary particles; number-based): Min = 11 nm, D25 = 25 nm, D50 = 34 nm, D75 = 48 nm, Max = 161 nm
Volume specific surface area: 150 m2/cm3
Zeta potential: -23.3 mV

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Key result

Dose descriptor:

LOAEL

Effect level:

<= 40 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

gross pathology

Remarks on result:

other: degeneration in stomach mucosa in females at all doses - cfr. Renaut et al 2022 under section 'Reproductive toxicity'

2

Key result

Dose descriptor:

NOAEL

Effect level:

>= 120 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other:

Remarks on result:

other: cfr. Renaut et al 2022 under section 'Reproductive toxicity'

Results (fetuses)

Effect levels (fetuses)

1

Key result

Dose descriptor:

NOAEL

Remarks:

F1 (cohort 2A)

Effect level:

ca. 40 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: neuropathology

Remarks on result:

other: cfr. Renaut et al 2022 under section 'Reproductive toxicity'

2

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 80 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other:

Remarks on result:

other: cfr. Renaut et al 2022 under section 'Reproductive toxicity'

Overall developmental toxicity

Key result

Developmental effects observed:

yes

Lowest effective dose / conc.:

40 mg/kg bw/day (nominal)

Treatment related:

yes

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified