Registration Dossier

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
multi-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline study with survival of offspring and gross morphological changes as the only parameters examined.
Principles of method if other than guideline:
The study was not conducted according to any guideline. For details on test procedure see below.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
water
Duration of treatment / exposure:
Exposure period: 12 weeks, between weaning and sexual maturity, each generation F0, F1, F2, F3 & F4
Premating exposure period (males): 12 weeks
Premating exposure period (females): 12 weeks
Duration of test: 2.5 years
Frequency of treatment:
continuous
Remarks:
Doses / Concentrations:
79 and 159 mg sodium silicate/kg body weight/d
Basis:

Control animals:
yes, concurrent no treatment
Statistics:
Chi-square Test
Dose descriptor:
NOAEL
Effect level:
> 159 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
mortality
Dose descriptor:
NOAEL
Generation:
F1
Sex:
male/female
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Reproductive effects observed:
not specified

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: 600 and 1200 mg SiO2/l in  drinking water, corresponding to 790 ppm

and 1580 ppm sodium silicate, respectively. This converts to 79 and 159 mg/kg bw/d on the assumption of  a mean body weight

of 200 g and a mean daily water consumption of 20 ml/d.


TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
-Parental data and F1: No effects on mortality, the only parameter  studied, were observed in the parental generation at any

dose level. Reduced pup survival was observed in the treatment groups.

- Mortality: No effects on length of life of the rats receiving sodium silicate in drinking water after weaning. Offspring from the

treatment  groups was frequently stillborn or small and weak, with survival limited  to only a few days. Cannibalism was prevalentamong females receiving  sodium silicate, especially among those receiving 1200 ppm.

The results from the 4 consecutive breedings are reported in the  publication as summed data only:

                              0          600       1200 ppm SiO2
-----------------------------------------------------------------
Number of matings         77          77           77
Number of litters             54          51           49
Total offspring born       517        346*        414*
Total offspring weaned  182        83*          44*

% of offspring weaned   35%       24%          11%
Difference, % of controls
   born                       -           67%          80%
   weaned                     -           46%          24%
-----------------------------------------------------------------
* Values differ from controls, P<0.001

- Offspring toxicity F1: 
- Litter size and weights: On average 9.6, 6.8 and 8.4 animals/litter (at 0, 600 and 1200 mg SiO2/l). No data on body weights
- Viability index: see table above
- Post natal survival until weaning: 35%, 24% and 11% (at 0, 600 and 1200 mg SiO2/l)
- Effects on offspring: Necrosis of the tail and of the feet as well in both treated groups. Litters were frequently stillborn or small and weak.

Additional information

In a 4-generation study with rats, the total number of offspring born at 79 mg/kg bw/d was reduced to 67% of offspring weaned to 46% of the control, respectively (Smith et al., 1973). The NOAEL for parental animals was determined to be > 159 mg/kg bw/day. For the F1 generation no NOAEL was identified. Severe limitations of the study and inter-current deaths, including controls make it however difficult to draw any firm conclusion from this study.

In addition, in oral repeated dose toxicity studies with rats and dogs, the macroscopic and microscopic examination of reproductive organs did not reveal any treatment-related effects (Newberne and Wilson, 1970). The NOAEL for rats and dogs was > 2400 mg/kg bw/day.

Kamboj and Kar (1964) did not find testicular effects of sodium silicate injected either subcutaneously or intratesticularly in male rats. The NOAEL was determined to be > 8 mg/kg bw.

Short description of key information:
NOAEL (rat) > 159 mg/kg bw/d

Effects on developmental toxicity

Description of key information
NOAEL (mouse) > 200 mg/kg bw/d
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
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.
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
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.
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
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
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.
Dose descriptor:
NOAEL
Effect level:
12.5 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 200 mg/kg bw/day
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: no advese, dose related effects have been observed
Abnormalities:
not specified
Developmental effects observed:
not specified

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.

Additional information

There are no data for sodium silicate. However, there are reliable data for the substance disodium metasilicate. Thus, read-across was performed based on a category approach.

 

In a non-standard study, disodium metasilicate was orally administered to pregnant mice from day 0 to 18 of gestation (Saiwai et al., 1980). Various examinations of fetuses and newborns were performed. No treatment-related effects were observed on body weight, organ weights or the number of pregnancies within all groups. Two dams died in the middle and high dose groups. The 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 the external 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.

Toxicity to reproduction: other studies

Link to relevant study records

Referenceopen allclose all

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline study with sufficient detail.
Principles of method if other than guideline:
Type: other: male reproduction organs
Method: other: no guideline was followed
GLP compliance:
no
Type of method:
in vivo
Species:
rat
Strain:
other: swiss albino
Sex:
male
Details on test animals and environmental conditions:
TEST ORGANISMS
- weight at study initiation: 100-120 g
Route of administration:
other: intratesticularly or subcutaneously
Vehicle:
water
Details on exposure:
- Total volume applied: 0.2 mL
Duration of treatment / exposure:
once
Frequency of treatment:
once
Duration of test:
7 days
Remarks:
Doses / Concentrations:
0.08 mmole/kg bw
Basis:

Control animals:
yes, concurrent vehicle
Dose descriptor:
NOAEL
Effect level:
0.08 other: mmole/kg bw
Sex:
male

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:  - Morphology: no alteration of the rat testis. - Histology: no alteration of the rat testis. - Organ weight: slight reduction in testis weight. - Spermatozoa: no effect on spermatozoa in the ductus deferens of the rats.

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 407
Principles of method if other than guideline:
Male and female reproduction organs were evaluated in a repeated dose toxicity study (28 days)
GLP compliance:
no
Type of method:
in vivo
Species:
other: dog
Strain:
other: Beagle
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
other: feed
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
ad libitum
Duration of test:
4 weeks
Remarks:
Doses / Concentrations:
2400 mg/kg bw/d
Basis:
nominal conc.
Control animals:
yes, concurrent vehicle
Dose descriptor:
NOAEL
Effect level:
2 400 mg/kg bw/day
Sex:
male/female

No effects on reproductive organs upon histopathological examination.

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guiddeline 407
Principles of method if other than guideline:
Male and female reproduction organs were evaluated in a repeated dose toxicity study (28 days)
GLP compliance:
no
Type of method:
in vivo
Species:
rat
Strain:
other: Charles River Cesarean-Derived (CD)
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
other: feed
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
ad libitum
Remarks:
Doses / Concentrations:
2400 mg/kg bw/d
Basis:
nominal conc.
Control animals:
yes, concurrent vehicle
Details on study design:
Duration of test: 4 weeks
Dose descriptor:
NOAEL
Effect level:
2 400 mg/kg bw/day
Sex:
male/female

No effects on reproductive organs upon histopathological examination.

Justification for classification or non-classification

The available data are conclusive but not sufficient for classification.