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Effects on fertility

Description of key information
NOAEL (rats, oral): 227 - 237 mg/kg bw/day
NOAEL (mice, oral): 260 - 284 mg/kg bw/day
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
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%).
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
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
Details on study schedule:
METHOD FOLLOWED:
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.
Remarks:
Doses / Concentrations:
79 and 159 mg sodium silicate/kg body weight/d
Basis:

Control animals:
yes, concurrent no treatment
Parental animals: Observations and examinations:
PARAMETERS ASSESSED DURING STUDY P AND F1:
- Clinical observations: Not executed
- Body weight: Not reported
- Estrous cycle: Not examined
- Sperm examination: Not executed
- Mortality: Examined, but frequency of observations not specified.

OFFSPRING: Gross morphological anomalies, stillbirths
Statistics:
Chi-square Test
Dose descriptor:
NOAEL
Effect level:
> 159 mg/kg bw/day
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 prevalent among 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

- 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

The available data on toxicity for reproduction are limited. In a 4-generation study, 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 conclusions from this study.

Short description of key information:
NOAEL (parental animals): 159 mg/kg bw
NOAEL (F1 generation): no NOAEL was identified

Toxicity to reproduction: other studies

Additional information

The available data on toxicity for reproduction are limited.

In oral repeated dose toxicity studies with rats (Ito et al.,1975)and mice (Saiwai et al.,1986) the macroscopic and microscopic examination of reproductive organs did not reveal treatment-related effects. The NOAEL for rats was > 227 - 237 mg/kg bw/day and for mice = 260 - 284 mg/kg bw/day.

Justification for classification or non-classification

Data are not sufficient for classification.

Additional information

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