Registration Dossier

Administrative data

Description of key information

No study is available on the reaction mass of calcium fluoride and calcium sulfate and calcium carbonate. However, reliable acute inhalation, oral and dermal toxicity studies are available on its three main constituents registered individually. None of the three main constituents are considered to be harmful by inhalation and oral route, and the dermal route is considered to be not relevant. Therefore, the reaction mass of calcium fluoride and calcium sulfate and calcium carbonate is also not considered to be hazardous by inhalation, oral or dermal routes.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Reliable LD50 results are available on the 3 individual constituents registered.
The LD50 of calcium fluoride and calcium carbonate were above 2000 mg/kg (no mortality observed). In a GLP-Acute toxicity study in rat exposed to calcium sulfate dihydrate by oral route the LD50 was above 2000 mg/kg (no mortality observed). The calculated LD50 of the anhydrous form is < 1581 mg/kg. It is however more likely that the reaction mass contains partially hydrated calcium sulfate.
When considering the experimental results on the constituents, the Acute Toxicity Estimate for the reaction mass can be calculated as > 2277 mg/kg.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Reliable LD50 results are available on the 3 individual constituents registered, tested individually at their respective maximum technically achievable concentration without inducing mortality or adverse clinical signs.
Therefore, no adverse effect are expected from acute inhalation exposure to the reaction mass.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The LD50 of the substance is based on the LD50 of Calcium carbonate determined in a GLP-Acute toxicity study in rat exposed to the nano form of calcium carbonate by dermal route

Additional information

Acute toxicity : oral route

A key study was identified for each of the three main constituents of the reaction mass substance. A study was performed according to the 423 OECD Guideline on the calcium fluoride (Cords & Lammer, 2010). Studies were performed according to the 420 OECD Guideline on the calcium sulfate dihydrate (NIER, 2003) and on the nano calcium carbonate (Bradshow, 2008). In these three studies, rats received a dose of 2000 mg/kg bw (limit test). No mortality and no clinical signs were observed in any case. Therefore, acute oral LD50 is considered to be higher than 2000 mg/kg bw for calcium fluoride and calcium carbonate, and higher than 1581 mg/kg bw for calcium sulfate anhydrous (ca. based on the LD50 of calcium sulfate dihydrate > 2000 mg/kg bw). Based on these available data, the worst-case value was chosen for the registered dossier. Hence, the acute oral LD50 of the reaction mass of calcium fluoride and calcium sulfate and calcium carbonate is considered to be higher than 1581 mg/kg bw.

Acute toxicity : inhalation

A key study was identified for each of the three main constituents of the reaction mass substance. Nose-only limit-test studies were performed according to the 403 OECD Guideline on the calcium fluoride (Mommers, 2002), the calcium sulfate dihydrate (Griffiths, 2010) and the nano calcium carbonate (Schuler, 2010). Rats were exposed for 4 hours up to 5.07 g/m3 for calcium fluoride, 3.26 mg/L for calcium sulfate dihydrate and 3 mg/L for nano calcium carbonate. These concentrations were the highest technically achievable. No mortality and no adverse clinical signs were observed in any case. Therefore, acute inhalation LC50 is considered to be higher than 5.07 g/m3 for calcium fluoride, higher than 3 mg/L for calcium carbonate, and higher than 2.61 mg/L for calcium sulfate anhydrous (ca. based on the LC50 of calcium sulfate dihydrate). Based on these available data, the worst-case value was chosen for the registered dossier. Hence, the acute inhalation LC50 of the reaction mass of calcium fluoride and calcium sulfate and calcium carbonate is considered to be higher than 2.61 mg/L (2610 mg/m3).

 

Acute toxicity : dermal route

A Key study was identified for the calcium carbonate, performed according to the OECD Guideline 402 (Bradshow, 2010). The nano calcium carbonate was applied as a paste in arachis oil to the skin of rats at a dose of 2000 mg/kg bw and covered with a semi-occlusive dressing for 24 hours. No death and no clinical signs of systemic effects were observed. The LD50 is considered to be higher than 2000 mg/kg bw.

Calcium fluoride and calcium sulfate are shown to be of inherently low toxicity by the oral and inhalation routes. Dermal absorption is also likely to be insignificant for this inorganic salt of low solubility, therefore it can be reliably predicted that the acute dermal toxicity of the substance will be very low. A study of acute dermal toxicity is scientifically unjustified and additionally cannot be supported for reasons of animal welfare.

Therefore, the acute dermal LD50 of the reaction mass of calcium fluoride and calcium sulfate and calcium carbonate is considered to be higher than 2000 mg/kg bw.

 

Justification for classification or non-classification

Harmonised classification

Reaction mass of calcium fluoride and calcium sulfate and calcium carbonate has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

 

Seulf classification

Based on the available data on its three main constituents, no additional self-classification is proposed regarding :

- Acute oral, dermal, and inhalation toxicity and,

- Specific target organ toxicity – single exposure

according to the Regulation (EC) No. 1272/2008 (CLP) as the studies were performed up to the highest recommanded doses or highest achievable concentrations.