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Description of key information

No studies are available with disodium disilicate (delta-crystalline). Read across to repeated dose toxicity studies with sodium silicate or sodium metasilicate ranging from 4 weeks to 180 days in rats, mice and dogs was done. The only treatment-related effects observed in rats were:
- polydipsia, polyuria and soft stools at 2400 mg/kg bw/day (sodium silicate of unspecified MR; 4 weeks exposure).
- Reduction of blood plasma Ca and Mg and liver Zn concentrations at 1259 mg/kg bw/day (sodium metasilicate, pentahydrate; 8 weeks exposure).
In female mice, a reduced pituitary gland weight was observed at 716 - 892 mg/kg bw/day (sodium metasilicate; 3 months exposure). Dogs exhibited gross cortical lesions of the kidneys, polydipsia, polyuria and soft faeces at 2400 mg/kg bw/day (sodium silicate of unspecified MR; 4 weeks exposure).
From these studies a NOAEL (180 days) of 159 mg/kg bw/day for rats was established.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
159 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Oral

No studies with disodium disilicate (delta-crystalline) are available for repeated dose exposure. 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 occurring and concentration levels are well controlled. Thus read across is justified in this case.

Repeated oral dose toxicity studies with soluble silicates ranging from 4 weeks to 6 months have been conducted with rats, mice and dogs.

The study by Smith (1973) was chosen as key study for risk assessment as it reveals the lowest NOAEL observed in the studies rated as reliable and relevant for risk assessment. Smith et al. (1973) exposed male and female rats (6/sex/group) to sodium silicate (MR 3.2) in drinking water for a period of 180 days. The animals were administered the equivalent of 600 and 1200 mg SiO2/L, corresponding to 78.9 and 158.7 mg sodium silicate/kg bw/day with a diet containing 0.1 to 1.0 % of SiO2 (based on dry weight). Body weight and mortality were the only parameters monitored. Statistically significant differences in body weight between experimental groups and controls were registered, but these were small (6 % or less), not consistent and not dose related. No mortalities were observed. After 180 days exposure, the male rats were used in a nitrogen and phosphorous retention study during a total of 17 days. Phosphorus retention was somewhat increased in the high dose group (approximately 12 %), while in the low dose group no effect of treatment was seen. Nitrogen retention was 50 % of controls in the lower dose group only. The NOAEL in rats after repeated oral administration of sodium silicate over 180 days was determined to be > 159 mg/kg bw/day.

Other supporting studies confirm the findings of the key study. The results are summarised below.

Newberne and Wilson (1970) fed 2400 mg sodium silicate/kg bw/day of unspecified molar ratio, to Beagle dogs (8/sex) and rats (15/sex) via the diet for a period of four weeks. The study design was similar to OECD guideline 407. Significant clinical observations were polydipsia, polyuria and soft stools in an unspecified number of dogs and rats. Body weight, food intake, and urinary and blood measurements were essentially normal in all animals. All chemical clinical tests were within normal limits. Gross cortical lesions of the kidney were observed in all male and 7/8 female dogs fed sodium silicate, but not in rats. Histopathological examination revealed irritation of the renal tubular epithelium followed by degenerative and regenerative changes and inflammatory cell infiltration into the interstitium. The NOAEL in rats and dogs after repeated oral administration of sodium silicate over 4 weeks was determined to be 2400 mg/kg bw/day.

Ito et al. (1975) conducted a 3-month toxicity study in rats (5/sex/group) with sodium metasilicate, administered via drinking water in concentrations of 200, 600 and 1800 mg/L (corresponding to approximately 26.4, 76.2 and 227.1 mg/kg bw/day for males and approximately 32.1, 97.6 and 237.2 mg/kg bw/day for females.). The study conditions were similar to OECD guideline 408. No clearly treatment related effects were found. The NOAEL in rats after repeated oral administration of sodium metasilicate over 90 days was determined to be 227 mg/kg bw/day.

In a 3-month feeding study reported by Saiwai et al. (1980), 10 mice/sex/dose were exposed to sodium metasilicate in the drinking water at concentrations of 300, 900 and 2700 ppm (males) and 333, 1000 and 3000 (females). This corresponds to 96 - 100, 264 - 280 and 776 - 832 mg/kg bw/day for males and 88 - 104, 260 - 284 and 716 - 892 mg/kg bw/day for females. Parameters examined were body weight, urinalysis, clinical chemistry, haematology, organ weights, and histopathology. No fatalities occurred. In females a significant decrease in pituitary glands weight was observed in the highest dose group. Other effects occasionally observed were single incidences and not dose-related. The NOAEL in mice after repeated oral administration of sodium metasilicate over 90 days was determined to be 260 mg/kg bw/day.

Kayongo-Male and Jia (1999) studied the effect of various silica sources added to diets of rats. Rats were exposed for 8 weeks to sodium metasilicate, pentahydrate at 500 ppm Si (corresponding to 1259 mg metasilicate/kg bw/day). Parameters examined were body weight, organ weight (liver and heart), hemoglobin, hematocrit, and mineral concentrations in blood plasma and organ tissues (liver and heart). No effects on body and organ weights were observed, whereas plasma Ca and Mg and liver Zn were reduced significantly. The NOAEL in rat after repeated oral administration of sodium metasilicate over 8 weeks was greater than 500 ppm Si.

The following studies are not reliable because of inconsistent and incomplete data. The credibility of these studies is questionable.

Treatment-related effects in mice which were orally administered disodium metasilicate up to 600 mg/kg bw/day for 14 days were lethargy, rough hair coat, dull fur, white, hazy spots on the horizontally neighbouring faces of the right internal lobe of the liver, a coarse kidney surface, localised bleeding in the thymus glands and thickened uterus linings. The NOAEL was determined to be 75 mg/kg bw/day (Saiwai et al., 1980). In rats, similar treatment-related effects were observed (Saiwai et al., 1980). For animals found dead during the study, bleeding in the stomach was reported. The NOAEL was calculated as 125 mg/kg bw/day. In rats administered disodium metasilicate via drinking water up to 110 mg/kg bw/day for 3 months, no mortalities and no clinical signs were observed (Sawai et al., 1980). However, a decrease of lymphocytes was noted and the protein content in the urine was increased in the high exposed animals. All other effects were not statistically significant. In contrast, rats which were administered the test item up to 50 mg/kg bw/day for 14 months, haematological parameters were changed, protein content in the urine was increased in the high exposed animals and organ weights of thyroid glands, livers, ovaries, hearts and brains were significantly affected (Sawai et al., 1980). No NOAELs were identified in both drinking studies. In the feeding study of Schwarz and Milne (1972), an unsuitable test system was used to investigate growth promoting effects of silicon in rats. Tooth pigmentation, hair loss, seborrhoea, loss of tonicity and an increased body weight gain were observed.

In conclusion, the NOAEL of 159 mg/kg bw/day from the study by Smith et al. (1973, rat, 180 days) was used for risk assessment.

Inhalation and Dermal

No repeated dose animal studies on the inhalation and dermal toxicity of silicates are available.

Justification for classification or non-classification

Based on the results of repeated oral toxicity testing, disodium disilicate (delta-crystalline) has not to be classified in regard of repeated dose toxicity according to Regulation 1272/2008/EC (CLP) and Directive 67/548/EC (DSD).