Synthetic amorphous magnesium silicate, with molar ratio (SiO2:MgO) range of 1.4-4

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Start: 15 October 1962

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Justification for type of information:

Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1963

Report date:

1963

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

yes

Remarks:

no complete one generation study according to current standards: too low number of animals and examinations, one dose only, dose selection unclear (relatively low dose selected).

Principles of method if other than guideline:

Method:
5 instead of 20 females, 1 male per 5 females (mating ratio 1:5 instead of 1:2); mating over 14 d, only 1 male used per treated and control group

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

Details on test material:

Aerosil, not further specified, hydrophilic: CAS-Name: Silica, amorphous, fumed, crystalline free, CAS-No. 112945-52-5

Specific details on test material used for the study:

Aerosil, not further specified, hydrophilic: CAS-Name: Silica, amorphous, fumed, crystalline free, CAS-No. 112945-52-5

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No further information

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

Exposure period: 6 months
Premating exposure period (males): 4.5 months
Premating exposure period (females): 4.5 months
Duration of test: 6 months

No further details

Details on mating procedure:

No further information available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure period: 6 months Premating exposure period (males): 4.5 months Premating exposure period (females): 4.5 months Duration of test: 6 months

Frequency of treatment:

daily

Details on study schedule:

Number of generation studies: 1

Doses / concentrations

Remarks:

Doses / Concentrations:
497 mg/kg bw (m); 509 mg/kg bw (f)
Basis:

No. of animals per sex per dose:

5 instead of 20 females, 1 male per 5 females

Control animals:

yes

Details on study design:

No further information

Examinations

Parental animals: Observations and examinations:

No data

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

No data

Litter observations:

No data

Postmortem examinations (parental animals):

No data

Postmortem examinations (offspring):

No data

Statistics:

No information available

Reproductive indices:

See "any other information field"

Offspring viability indices:

See "any other information field"

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Details on results (P0)

Parents: No clinical symptoms; no mortality,no abnormalities in  body-weight gain and feed consumption, no haematological findings.  

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

497 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Concentration tested in males

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

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

Details on results (F1)

In pups during lactation [total: 45 and 37 (control), resp.], no behavioral or developmental or structural abnormalities

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

497 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Concentration tested in males (P0)

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Result: negative

Parents: No clinical symptoms; no mortality,no abnormalities in  body-weight gain and feed consumption, no haematological findings.
 
In pups during lactation [total: 45 and 37 (control),
resp.], no behavioral or developmental or structural
abnormalities.
  --------

Applicant's summary and conclusion

Conclusions:

No adverse effects observed in dams or offspring up to 497 mg/kg bw/day

Executive summary:

A reproductive study was conducted using Aerosil based on OECD test guideline 415. There were no clinical symptoms; mortality, abnormalities in body-weight gain and feed consumption or no haematological findings in the parents.  There were no behavioural or developmental or structural abnormalities in pups during lactation. The NOAEL for P0 and F1 generation was determined to be 497 mg/kg bw/day.