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Administrative data

Description of key information

For Ettringite:
No acute oral or dermal toxicity was observed up to the highest tested doses. LD50 (oral)/ LD50 (dermal): > 2000 mg/kg bw.
Further data and assessment from CaSO4 according to justification for read across (see separate document in iuclid chapter 13).
LD50 (dihydrate, mouse, oral) = 4704 mg/kg bw
LD50 (hemihydrate, mouse, oral) = 5824 mg/kg bw
LD50 (dihydrate, rat, oral) = 9934 mg/kg bw
LD50 (hemihydrate, rat, oral) = 9934 mg/kg bw
NOEC (Inhalation) = 3.26 mg/L calcium sulphate dihydrate
In the registration dossier of CaSO4 is stated:
Calcium sulfate is not considered to be harmful by the oral or inhalation route. The dermal toxicity of calcium sulfate is not considered to be relevant. Calcium sulfate is an inorganic ionic solid and is not expected to penetrate the skin. Furthermore, calcium sulfate is commonly used in plaster of Paris, and is not known to have been associated with any toxic effects.

Key value for chemical safety assessment

Additional information

In the registration dossier of CaSO4 is stated:

Acute toxicity: Oral route

In a reliable OECD guideline study (NIER 2003) calcium sulfate dihydrate was administered by gavage at 2,000 mg/kg bw to 4 female rats. Rats were observed for clinical signs and mortality for 14 days. No dead animals were observed in the limit test after 14 days observation so the oral LD50 for rats was > 2000 mg/kg bw. Based on this result the oral LD50 of calcium sulfate anhydrous is >1581 mg/kg b.w.

Khodykina 1996 (supporting study): Calcium sulphate (either as dihydrate or as hemihydrate) was administered to mice and rats by oral gavage. The following LD50 values were determined:

LD50 (dihydrate, mouse, oral) = 4704 mg/kg bw

LD50 (hemihydrate, mouse, oral) = 5824 mg/kg bw

LD50 (dihydrate, rat, oral) = 9934 mg/kg bw

LD50 (hemihydrate, rat, oral) = 9934 mg/kg bw

In the key study (NIER 2003), neither mortality nor any signs of systemic toxicity were observed after single oral administration of calcium sulphate dihydrate up to a maximum concentration of 2000 mg/kg bw to rats. Khodykina et al. (1996) have administered calcium sulphate (either as dihydrate or hemihydrate) in much higher concentrations (up to 10000 mg/kg bw) to both rats and mice. For either substance, animal and route of administration, the determined LD50 values were >4000 mg/kg bw, in fact doubling the requested benchmark dose for toxicity classification.

It can therefore be stated that calcium sulphate in either form can be regarded as non-toxic.

Acute toxicity: Inhalation route

In the current study, no signs of systemic toxicity were observed in rats up to a concentration of 3.26 mg/L calcium sulphate dihydrate.

It is recognised that the mean achieved atmosphere concentration is lower than 5 mg/L which is the required concentration for classification and labelling. During characterisation, the generation system was adapted to maximise the amount of particles <4 μm, as recommended by OECD (Series on Testing and Assessment Number 39: Guidance Document on Acute Inhalation Toxicity Testing, p37): “When testing aerosols, the primary goal should be to achieve a respirable particle size (MMAD of 1-4 μm). This is possible with most test articles at a concentration of 2 mg/L. Aerosol testing at greater than 2 mg/L should only be attempted if a respirable particle size can be achieved” and EC Guidelines (Regulation EC No. 1272/2008 section 3.1.2.3.2.): “Inhaled particles between 1 and 4 microns mean mass aerodynamic diameter (MMAD) will deposit in all regions of the rat respiratory tract. […] In order to achieve applicability of animal experiments to human exposure, dusts and mists would ideally be tested in this range in rats.”

Using a higher concentration of total dust would have led to a lower amount or respirable (<4 µm) particles. It can therefore be estimated that also at higher particle concentrations no toxicity after inhalation exposure has to be expected

Acute toxicity: Dermal route.

Calcium sulfate is an inorganic ionic solid. It is expected to partition strongly to water rather than organic media. While it is not possible to measure or accurately predict an octanol/water partition coefficient for inorganic ionic substance, such a value would be expected to be very low. Electrolytes are also known not to penetrate the skin in any significant quantity. Given the physico-chemical properties of CaSO4, it is not expected that the substance would penetrate the skin in any significant quantity and so would therefore not cause any toxic effects following acute dermal exposure.

Furthermore, plaster of Paris, containing mainly the hemihydrous calcium sulfate, has been used in the immobilization of broken bones and is not known to have been associated with any toxic effects, despite intimate skin contact, for periods of the order of one month, over considerable areas of skin. As this use simulates the acute dermal toxicity, it can safely be inferred that an acute dermal exposure test would be unlikely to cause any toxic effects.

Justification for classification or non-classification

Classification according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC and subsequent regulations

- No classification needed: the data are conclusive but not sufficient for classification.

In the registration dossier of CaSO4 is stated:

Acute oral:

The acute oral toxicity of calcium sulphate was determined in two different studies. NIER 2003 found that the LD50 of calcium sulphate dihydrate after single oral application to rats is >2000 mg/kg bw. Khodykina et al. (1996) have administered much higher concentrations and found LD50 values >4000 mg/kg bw in both, rats and mice.It can therefore be stated that calcium sulphate in either form can be regarded as non-toxic and no classification is needed

Acute inhalation:

Although the current experiment does not reach the dust concentrations for classification according to Regulation EC 1272/2008 (max. limit dose of 5 mg/L) conditions were altered to achieve a maximum concentration of respirable particles (<4 µm). It can therefore be concluded that, even at higher dust concentrations, no systemic toxicity would arise.Taking into account the OECD Guidance Document on Acute Inhalation Toxicity Testing as well as Regulation EC No. 1272/2008, no classification of calcium sulphate as toxic by inhalation is justified

Acute dermal:

Calcium sulfate is an inorganic ionic solid not likely to penetrate the skin in any significant quantity. Furthermore, orthopaedic gypsum casts can be deemed to simulate acute dermal toxicity study conditions, are used for longtime without noticed any toxic effects. Therefore, it can safely be inferred that acute dermal exposure would be unlikely to cause any systemic toxic effects and therefore no classification for dermal toxicity is justified