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Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Silicon dioxide
EC Number:
231-545-4
EC Name:
Silicon dioxide
Cas Number:
7631-86-9
Molecular formula:
O2Si
IUPAC Name:
Silicon dioxide
Test material form:
solid
Specific details on test material used for the study:
NM-200, synthetic amorphous silicon dioxide, precipitated. Cas number: 112926-00-8.

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
Wistar outbred (Crl:WI(Han) strain.
Sex:
male/female
Details on test animals or test system and environmental conditions:
According to the authors, conditions in the animal room were kept under standard laboratory conditions.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Methylhydroxypropylcellulose (MHCP)
Details on exposure:


DIET PREPARATION
- Rate of preparation of diet (frequency): Once weekly
- Mixing appropriate amounts with (Type of food): Rodent breeding diet
- Storage temperature of food: Ambient temperature

VEHICLE
- Justification for use and choice of vehicle (if other than water): Not specified
- Concentration in vehicle: 0.5 % v/v of MHPC in Ultrapure water
- Amount of vehicle (if gavage): Not specified
- Lot/batch no. (if required): Not specified
- Purity:Not specified
Details on mating procedure:
- M/F ratio per cage: 1 M/1 F
- Length of cohabitation: 2 weeks mating period
- Proof of pregnancy: sperm in vaginal smear, referred to as day 0 of gestation
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males were exposed during a 10 week pre-mating period, during mating and up to the day before termination. Females were exposed during a 10 week pre-mating period, during mating, gestation and lactation up to postnatal day 21. F1-pups were dose from postnatal day 22 until termination.
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
Control animals:
yes

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Description (incidence and severity):
According to the authors, synthetic amorphous silica NM-200 had no effects on reproduction of the parental F0 and F1 animals.

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: See "Remarks"
Remarks on result:
other: See "Remarks"
Remarks:
The study concludes that synthetic amorphous silica NM-200 generated no effects on reproduction of F0 and F1 generations nor had any developmental effects on the F1 and F2 pups, nor on the sexual maturation of the F1 weanlings.

Target system / organ toxicity (P0)

Key result
Critical effects observed:
no

Results: P1 (second parental generation)

Effect levels (P1)

Basis for effect level:
other: See "Remarks"
Remarks on result:
other: See "Remarks"
Remarks:
The study evaluated the reproduction toxicity of synthetic amorphous silica in rats over two generations. Included in the study were a F0-, F1- and a F2-generation.

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
A statistically significant decreased relative weight of the thyroid of the male animals of the mid-dose group of the F1-
generation was observed.
Gross pathological findings:
not specified
Histopathological findings:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
other: According to the authors, the No Observed Adverse Effect Level (NOAEL) was established at 1000 mg/kg body weight per day. No toxicological-relevant differences were observed in exposed rats compared to controls in any generation.
Effect level:
1 000 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: See "Remarks"
Remarks on result:
other: See "Remarks"
Remarks:
The study concludes that synthetic amorphous silica NM-200 generated no effects on reproduction of F0 and F1 generations nor had any developmental effects on the F1 and F2 pups, nor on the sexual maturation of the F1 weanlings.

Target system / organ toxicity (F1)

Key result
Critical effects observed:
no

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
no effects observed
Description (incidence and severity):
No effects on the development of the F2 pups.

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Key result
Dose descriptor:
NOAEL
Remarks:
According to the authors, the No Observed Adverse Effect Level (NOAEL) was established at 1000 mg/kg body weight per day. No toxicological-relevant differences were observed in exposed rats compared to controls in any generation.
Generation:
F2
Effect level:
1 000 mg/kg bw/day
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: See "Remarks"
Remarks on result:
other: See "Remarks"
Remarks:
The study concludes that synthetic amorphous silica NM-200 generated no effects on reproduction of F0 and F1 generations nor had any developmental effects on the F1 and F2 pups, nor on the sexual maturation of the F1 weanlings.

Target system / organ toxicity (F2)

Key result
Critical effects observed:
no

Overall reproductive toxicity

Key result
Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
The study concludes that synthetic amorphous silica NM-200 generated no effects on reproduction of F0 and F1 generations nor had any developmental effects on the F1 and F2 pups, nor on the sexual maturation of the F1 weanlings. The NOAEL was found to be at 1000 mg/kg body weight per day.
Executive summary:

An oral two-generation reproduction toxicity study with synthetic amorphous silicon dioxide (NM-200) was performe with Wistar rats. Animals were exposed to 100, 300 and 1000 mg/kg body weight/day by gavage. Male animals were exposed during a 10 -week premating period and during mating and to the day of sacrifice. Females were exposed during a 10 -week premating period and during mating, gestation and lactation up to postnatal day 21. Selected F1 -pups were exposed from postnatal day 22 and up to the day of sacrifice. Throughout the study the animals were daily checked for clinical signs and abnormal behaviour. Taken together, exposure to synthetic amorphous silica Nm-200 over two generations at concentrations up to 1000 mg/kg body weight/day had no effects on reproduction of the parental F0 and F1 generations nor on the development of the F1 and F2 pups, nor on the sexual maturation of the F1 weanlings. The NOAEL was found to be at 1000 mg/kg body weight per day.