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Description of key information

The test substance disodium disilicate (delta-crystalline) was examined in an acute oral toxicity study and in two inhalation toxicity studies in rats. The inhalation toxicity studies included an acute inhalation toxicity study in which the rats were exposed to the test substance as aerosol via the nose for 4 hours followed by a 22 day observation period and a 3-day whole-body inhalation study in which the rats were exposed to the test substance as dust for 6 hours per day for 3 days followed by an observation period of 14 days. No biochemical/cytological changes in the bronchoalveolar lavage fluid (BALF) were observed in the 3-day whole-body inhalation study and the following toxicological endpoints obtained from the 3 studies assisted in the test substance classification: 
Oral LD50 male animals: 2507 mg/kg bw
Oral LD50: female animals 2000-3150 mg/kg bw
Inhalation LC50 male and female rats > 3.5 mg/L
Inhalation NOEL male rats: 10.8 mg/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
10.8 mg/m³ air

Additional information

Acute toxicity: oral

In an acute oral toxicity study (94.0711) 4 groups of male and 3 groups of female Wistar rats (5 rats in a group), at an approximate age of 7 to 8 weeks, weighing (mean weight) of 189 g (male animals) and 178 g (female animals) were administered by gavage with a single oral dose of 1250 (only for male rats), 2000, 3150 and 5000 mg/kg body weight of the test substance, disodium disilicate (delta-crystalline). The animals were observed up to 28 or 35 days.

Mortality occurred in the 2000 mg/kg bw dose group (only in male animals) and in higher dose groups of both sexes. Different clinical signs of intoxification were observed in animals of the lowest dose group and onwards. Most of the surviving animals were free from clinical signs of intoxication after 8- 14 days but symptoms of stilted gait and sunken flanks were observed in individual animals until the end of the observation period. Development of body weight was impaired in all dose groups. After the animals were sacrificed at the end of the observation period, the gross pathology examination showed partial fusion of liver lobules and parts of the small intestine with the stomach. The stomach wall was indurated and showed white or black discolouration.

The worst case LD50 values were determined as:

Oral LD50 male animals: 2507 mg/kg bw

Oral LD50 female animals: 2000-3150 mg/kg bw.

The study was conducted according to the OECD guideline 401 (adopted: 1981-05-12).

Acute inhalation toxicity studies

Two inhalation toxicity studies in rats were conducted with the test substance disodium disilicate (delta-crystalline): A classical acute inhalation study (study no.: 272406) which was conducted according to the OECD guideline 403 and the EU method B.2 and a 3-day whole- body inhalation (study no.: 98-6122)

• In the acute inhalation toxicity study (study no.: 272406) 5 male and 5 female Wistar rats (males: 8-10 weeks old, mean weight, 221.5 g and females: 10-12 weeks, mean weight, 195.4 g) were exposed for 4 hours to disodium disilicate (delta-crystalline) by a single administration via the inhalation route (nose only, aerosol) to a mean concentration of 3.51 mg/L air (corresponding to 3510 mg/m³ air) of the test substance (the highest technically achievable concentration). Following the exposure period the animals were observed for 22 days for clinical signs, body weights and mortality. All animals were necropsied and subjected to gross macroscopic examination. One female rat died on test-day 9. Several clinical signs were observed during the three-week observation period and some gross pathology findings were found in the macroscopic observations after necropsy (which should be re-examined for substance-related effects in a subchronic assay). In this acute 4-hour inhalation toxicity study a LC50 greater than 3.51 mg/ L air (corresponding to 3510 mg/m³ air) was estimated for male and female rats.

• The 3-day whole-body inhalation study was intended to estimate the pulmonary toxicologic potential of the test material disodium disilicate (delta-crystalline) by evaluation of the biochemical/cytological changes in the bronchoalveolar lavage fluid (BALF) in 10 male Fischer F-344 rats, exposed to the test substance for six hours per day for 3 days at a targeted concentration of 10 mg/m3 air administered as dust by an whole-body inhalation. At the end of the exposure period the animals were observed for another 14 days (recovery period). An air control group of 5 male rats was exposed to clean air only. The mean gravimetric exposure concentrations were determined to be 0.00± 0.00 and 10.8 ± 2.6 mg/m3 air, for air control and test material, respectively. Particle size distribution determinations (average mass median aerodynamic diameter of 2.4 microns for the test material exposed group), indicated that a respirable concentration was administered to the test animals. Results of the air control exposures showed that there was no aerosol present.

All animals survived the exposure time and the 14-day post-exposure observation period. There were no clinical signs of treatment noted during the exposure period or during the post-exposure observation period in either group. There were no significant differences in body weights.

Bronchoalveolar lavage was performed one day after the last exposure (both groups) and 14 days after the last exposure (disodium disilicate (delta-crystalline) group). The animals were then discarded without further evaluation.There were no significant differences in BALF results at the first lavage interval. At the second lavage interval there was no basis for comparison, since all control animals were sacrificed at the first lavage interval.

In conclusion, three consecutive exposures of rats to disodium disilicate (delta-crystalline) at 10.8 mg/m3 air produced no significant biochemical or cytological changes in bronchoalveolar lavage fluid as compared to the air control animals. Therefore, under the conditions of this study, 10.8 mg/m3 air was considered to be the NOEL.

Justification for classification or non-classification

The LC50 value derived from the acute inhalation toxicity study was greater than 3.51 mg/L, which directs to grouping the test substance in category 4 (1.0 < category 4 ≤ 5.0). As the measured dose in the acute inhalation study (3.51 mg/L air) was the highest technically achievable concentration and the real LC50 value is assumable higher, the test substance should be categorized as not classified. Additionally, the findings of the acute oral toxicity study (LD50≥2000 mg/kg bw) do support a categorization of not classified.

Hence, altogether the test substance disodium disilicate (delta-crystalline) is not classified for acute toxic effects according to 67/548/EEC (DSD) and 1277272008/EC (CLP/GHS).

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