Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
multi-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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. For justification of read across see endpoint summary.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Effects of soluble silica on growth, nutrient balance and reproductive performance of albino rats.
Author:
Smith, G. S. et al.
Year:
1973
Bibliographic source:
J. Animal Sc. 36, 271-278
Reference Type:
secondary source
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Non-guideline study with survival of offspring and gross morphological changes as the only parameters examined.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Silicic acid, sodium salt
EC Number:
215-687-4
EC Name:
Silicic acid, sodium salt
Cas Number:
1344-09-8
IUPAC Name:
sodium hydroxy(oxo)silanolate
Details on test material:
SOURCE: Diamond Alkali Company, Cleveland, Ohio, USA
PURITY: Not reported
IMPURITY/ADDITIVE/ETC.: Not reported
ANY OTHER INFORMATION: Molar ratio 3.2

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
All animals were maintained on a normal diet (which contained 0.1 to 1.0% of SiO2 (based on dry weight). Housing conditions of the animals were not optimal, so that even in the control group survival of offspring until weaning was poor (35%). 

Administration / exposure

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
Doses / concentrations
Remarks:
Doses / Concentrations:
79 and 159 mg sodium silicate/kg body weight/d
Basis:

Control animals:
yes, concurrent no treatment
Details on study design:
Rats were treated with 0, 600 and 1200 mg SiO2/l drinking water from weaning age (3 weeks) to maturity (4 months). Six  males and six females were then mated in each treatment group. Offspring  from the control group were distributed among all water treatments upon  weaning (3 weeks of age) -nine additional males and nine additional  females were thereby added to each treatment group- and upon attainment of maturity these rats were also mated within their treatment groups. This process whereby offspring from control groups were distributed among  treatments was repeated three times during a period of 2.5 years, and the  mating procedure was repeated at four separate phases during the overall  study, thereby providing data from 77 matings involving 59 females for  each of the three treatments in the overall study.

Examinations

Parental animals: Observations and examinations:
PARAMETERS ASSESSED DURING STUDY P AND F1: 
- Clinical observations: Not executed
- Body weight: Not reported
- Mortality: Examined, but frequency of observations not specified.
Oestrous cyclicity (parental animals):
- Estrous cycle: Not examined
Sperm parameters (parental animals):
- Sperm examination: Not executed
Litter observations:
OFFSPRING: Gross morphological anomalies, stillbirths
Statistics:
Chi-square Test

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

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.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
> 159 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
mortality
Remarks on result:
other: no mortality observed a the high dose

Results: F1 generation

Details on results (F1)

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 below
- 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.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Sex:
male/female
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

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.


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

Applicant's summary and conclusion

Conclusions:
In a 4-generation study, Smith et al. (1973) assessed the effect of sodium silicate administered via drinking water to rats. Due to the limitations of the study only a NOAEL for parentaral toxicity (> 159 mg/kg bw/day) can be derived. For the F1 generation no NOAEL was identified.
Executive summary:

In a 4-generation study, Smith et al. (1973) assessed the effect of sodium silicate administered via drinking water to rats. The exposure concentration was 600 and 1200 mg SiO2/L, corresponding to 79 and 159 mg sodium silicate/kg bw/d from weaning until mating. Control groups received no sodium silicate in their drinking water. For 4 consecutive generations, the rats were mated and the total number of offspring analysed. No dose-related effect on litter number up to and including 159 mg/kg bw/d was observed. Survival of offspring until weaning was poor, even in the controls (35, 24, and 11 % at 0, 79, 159 mg/kg bw/d, respectively). The total number of offspring born was reduced to 67 % of the controls at 79 mg/kg bw/d and to 80 % at 159 mg/kg bw/d. Litters born to females receiving silicate were frequently stillborn or small and weak, with survival limited to only a few days. In addition, cannibalism was prevalent and necrosis of the tail and occasionally the feet was observed in offspring of silicate-treated animals. Due to the limitations of the study (also severe effects in control animals e.g. inter-current deaths, no dose-response relationship for total offspring born) makes it however difficult to draw any firm conclusions from this study. Thus a NOAEL can only be derived for parentaral toxicity (> 159 mg/kg bw/day). For the F1 generation no NOAEL was identified.