Disodium disilicate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No studies are available with disodium disilicate (delta-crystalline). Read across to reproduction toxicity studies with sodium silicate or sodium metasilicate was done instead.
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.
In oral repeated dose toxicity studies with rats, mice and dogs, the macroscopic and microscopic examination of reproductive organs did not reveal any treatment-related effects (refer also to IUCLID5 section 7.5.1).

Additional information

No studies with disodium disilicate (delta-crystalline) are avaialble for reproduction toxicity tests. Read across to soluble silicates (sodium silicate) was done due to the fact, that the substances are almost identical. Disodium disilicate (delta-crystalline) differs from the soluble silicates only in the crystal structure and the molar ratio of sodium and silicate. When dissolved in water so called waterglas is formed from all 3 components. In the human body (water based system) silicates are naturally occurring and concentration levels are well controlled. Thus, read across is justified in this case.

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 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. However, the limitations of the study (severe effects in control animals e.g. inter-current deaths, no dose-response relationship for total offspring born) make it difficult to draw any firm conclusions. Thus a NOAEL can only be derived for parental toxicity (> 159 mg/kg bw/day). For the F1 generation no NOAEL was identified.

From the available 4 generation study, no clear conclusion can be drawn with regard to fertility. From the available 4 generation study, no clear conclusion can be drawn with regard to fertility. However, Kamboj and Kar (1964) examined the effects of sodium silicate on morphology, histology and weight on testis as well as spermatozoa in the ductus deferens. They did not find any effects of subcutaneously or intratesticularly injected sodium silicate in male rats. The NOAEL was determined to be > 8 mg/kg bw. In addition, in oral repeated dose toxicity studies with rats, mice, and dogs, the macroscopic and microscopic examination of reproductive organs did not reveal any treatment-related effects (see toxicity to reporoduction: other studies). Thus, from the available data it can be concluded, that soluble silicates and consequently disodium disilicate (delta-crystalline) do not have adverse effects on fertility.

Short description of key information:
No studies are available with disodium disilicate (delta-crystalline). Read across to a reproduction toxicity study with sodium silicate was done instead.
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 parental toxicity (> 159 mg/kg bw/day) can be derived. For the F1 generation no NOAEL was identified.

Effects on developmental toxicity

Description of key information

No studies are available with disodium disilicate (delta-crystalline). Read across to a developmental toxicity study with sodium metasilicate was done instead.
In a develpmental toxicity study with mice, no developmental effects were observed up to and including 200 mg/kg bw/day disodium metasilicate at which systemic toxicity was clearly shown. The NOAEL for developmental toxicity was determined to be > 200 mg/kg bw. The NOAEL for maternal toxicity was 12.5 mg/kg bw/day. 

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

200 mg/kg bw/day

Additional information

No studies with disodium disilicate (delta-crystalline) are avaialble for developmental toxicity tests. Read across to soluble silicates (sodium metasilicate) was done due to the fact, that the substances are almost identical. Disodium disilicate (delta-crystalline) differs from the soluble silicates only in the crystal structure and the molar ratio of sodium and silicate. When dissolved in water socalled waterglas is formed from all 3 components. In the human body (water based system) silicates are naturally occuring and concentration levels are well controlled. Thus, read across is justified in this case.

In a developmental toxicity study by Saiwai et al. (1980), pregnant mice were administered 12.5, 50 or 200 mg/kg bw/d sodium metasilicate in aqueous solution from day 0 until 17/18 of gestation by daily gavage. Among the mother animals 2 fatalities occurred both in the 50 and 200 mg/kg group (total number of animals: 33 and 27, respectively); body and organ weights and dissection findings were not affected. On day 18 of gestation foetuses were delivered by hysterectomy and examined. No differences to controls were observed for the following parameters: number of pregnancies and living or dead foetuses, body weight and malformations of inner organs and the skeleton. 10 mother animals were allowed to deliver their young naturally. The neonates were observed for 30 days. Litter size and fertility index were not significantly affected up to and including 200 mg/kg bw/d. Body weight gain, organ weights and behavioural development did not reveal any differences to the control. Skeletal malformations did not exhibit a correlation with dosage.

Toxicity to reproduction: other studies

Additional information

No studies with disodium disilicate (delta-crystalline) are available for other reproduction toxicity tests. Read across to soluble silicates (sodium silicate and sodium metasilicate) was done due to the fact, that the substances are almost identical. Disodium disilicate (delta-crystalline) differs from the soluble silicates only in the crystal structure and the molar ratio of sodium and silicate. When dissolved in water so called waterglas is formed from all 3 components. In the human body (water based system) silicates are naturally occuring and concentration levels are well controlled. Thus, read across is justified in this case.

In a study by Kamboj and Kar (1964), male rats were injected subcutaneously and intratesticularly with doses of 0.08 mmole/kg sodium silicate. When the testes were examined 7 d after injection, no morphological or histological effects were seen in either application route nor was there any effect on residual spermatozoa in the ductus deferens. Testicular weight was slightly reduced as compared to controls injected with sterile water.

Some of the available subchronic/chronic repeated dose studies (see IUCLID6 section 7.5.1) shed also light on the effects of sodium silicates on the reproductive organs:

In the 3-months study performed by Sawai et al. (1980) with mice, exposure via drinking water to metasilicate concentrations up to and including 832 and 892 mg/kg bw/d for males and females, respectively, did not show treatment-related effects on the pathohistology of testes and ovaries. The mean wet weight of these organs was also not affected (testes: 0.13 - 0.14 g for control; 0.12 - 0.14 g for dosage groups; ovaries: 7.3 - 8.4 g for control; 7.4 - 9.7 g for dosage groups).

No effects on the male and female reproductive organs were observed upon macroscopic and microscopic examination when rats were exposed to 200, 600 and 1800 ppm in drinking water (26, 76 and 227 mg/kg bw/d for males; 32, 98 and 237 mg/kg bw/d for females) for 3 months (Ito et al. 1975).

Rats and beagle dogs were exposed to sodium silicate of unknown molar ratio for 4 weeks at a single concentration of 2400 mg/kg bw/d via the diet. According to the authors, a complete necropsy and histopathological study was performed and no treatment-related effects except in the kidneys observed (Newberne and Wilson 1970).

Justification for classification or non-classification

From the available 4 -generation study no clear conclusion with regard to fertility reproductive effects can be drawn. However, in repeated dose toxicity studies with rats, mice and dogs the macroscopic and microscopic examination of reproductive organs did not reveal treatment-related effects. In addition, no adverse effects on testes of sodium silicate injected either subcutaneously or intratesticularly in male rats were observed.

Furthermore, in a developmental toxicity study in mice, litter size and fertility index were unaffected at sodium metasilicate concentrations up to and including 200 mg/kg bw/d. No developmental effects were observed in this study up to and including 200 mg/kg bw/d.

Thus, in conclusion taken all available data together, disodium disilicate (delta-crystalline) has not to be classified with regard of reproduction toxicity (development or fertility) according to Regulation 1272/2008/EC (CLP) and Directive 67/548/EC (DSD).