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Toxicological information

Developmental toxicity / teratogenicity

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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)

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
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)

open allclose all
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'

Results (fetuses)

Effect levels (fetuses)

open allclose all
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'

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

Applicant's summary and conclusion