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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No tables provided with report; results only discussed qualitatively. Therefore, limited amount of information available.
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Safety of the metal scavengers sodium metasilicate and sodium polyphosphate.
Author:
Saiwai, K. et al.
Year:
1980
Bibliographic source:
Internal Report Toho University
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Principles of method if other than guideline:
Application of Na-metasilicate via gavage from day 0 to 18 of gestation. Examination of fetuses and and newborns.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SOURCE: not reported
PURITY: not reported
IMPURITY/ADDITIVE/ETC.: not reported
ANY OTHER INFORMATION: the test substance was sodium metasilicate, 20% aqueous solution.

Test animals

Species:
mouse
Strain:
other: JLC-TCR
Details on test animals and environmental conditions:
Well developed males and females 8-13 weeks of age and  27-35 g/animal.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
17-18 days
Frequency of treatment:
daily
Duration of test:
18 days
Doses / concentrations
Remarks:
Doses / Concentrations:
12.5, 50 or 200 mg/kg bw/d
Basis:
nominal conc.
Control animals:
yes
Details on study design:
Sex: male/female

Examinations

Maternal examinations:
body weight
Ovaries and uterine content:
counting of nidations, corpi lutei and living/dead fetuses
Fetal examinations:
weighing of living fetuses and important organs, sex determination, examination of integument anomalies, naked eye  examination of other changes
Parameters evaluated were: number of neonates, parturition failures, body weight gain, behavioral development in the Running
and Rod Grasping Test (see below) and skeletal development.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
12.5 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Key result
Dose descriptor:
NOAEL
Effect level:
> 200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Any other information on results incl. tables

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Parental data and F1: 
- Body weight: no treatment-related effects were observed in either mother animals, fetuses delivered by hysterectomy or

neonates. 

- Fertility index: 
Dose [mg/kg bw/d] pregnancies/mated female    % pregnancies
---------------------------------------------------------------
     0 (control)             20/26                   77%
    12.5                      22/24                   92%
    50                        20/31                   65%
   200                        21/25                   84%

- Duration of gestation: 18 days

- Mortality: 2/27 females administered 50 mg/kg and 2/33 females administered 200 mg/kg died during the exposure period. In

one female of  the highest dose group all fetuses died at an early stage. No parturition  fatalities were observed when mothers

were allowed to deliver their young  naturally. 
- Gross pathology incidence and severity: observed skeletal malformations  in neonates like cervical vertebrae, tail vertebrae

and vomer adhesion  occurred in the controls, too, and did not show a dosage correlation. No  malformations of the skeleton or

the inner organs of fetuses delivered by  hysterectomy were observed; the frequency of malformations and  abnormalities of theexternal integument, like opened eyes, cleft palate  and exencephaly showed a slight tendency toward dose dependance, but it  was lower than in the control. No effects on main organs of both mothers and neonates as compared to controls.
- Number of corpora lutea: No significant differences between control and  test groups, but actual numbers not reported.
- Organ weight changes: No treatment-related effects of organ weights of  mother animals and neonates; not reported for

fetuses delivered by hysterectomy.


- Offspring toxicity F1: 
- Litter size and weights: There was a dose-related, but not  statistically significant decrease in litter size.
Dose [mg/kg bw/d]    average no. of neonates/litter
-----------------------------------------------------
     0 (control)            14.7 +- 2.4
    12.5                      13.8 +- 2
    50                        12.9 +- 2
   200                        12.8 +- 2

- Post natal survival until weaning: no treatment-related effects on body  weight gain. 
- Effects on offspring: a dose-related, but not statistically significant  decrease in embryo weight and delayed
ossification process was observed.
- Postnatal growth, growth rate: no treatment related effects
- Other observations: no treatment-related effects in the Running Test  and the Rod Grasping Test.

Applicant's summary and conclusion