Strontium carbonate

Endpoint summary

Description of key information

Acute toxicity, oral: LD50 > 1395 mg/kg bw (> 828 mg Sr/kg bw)
Acute toxicity, inhalation: LD50 > 5 mg/L
Acute toxicity, dermal: data waiving

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment in Section 13.

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD50

Effect level:

> 828 mg/kg bw

Based on:

element

Remarks:

Sr

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the read-across from Strontium nitrate, the oral LD50 value for Strontium carbonate corresponds to > 1395 mg/kg body weight in Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 1 395 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included as attachment in Section 13.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the read-across from Strontium nitrate, the inhalatory LD50 (4h) value of Strontium carbonate was considered to exceed 5 mg/L in Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 5 mg/L air

Physical form:

inhalation: aerosol

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Acute dermal toxicity study does not need to be performed since an acute inhalation toxicity study is available. According to the data requirements as outlined in Annexes VII-VIII, 8.5 of Regulation (EC) 1907/2006 the choice for the second route of exposure shall depend on the likely route of human exposure. The inhalation route is considered as the major route of exposure.

Conclusions:

Acute dermal toxicity study does not need to be performed since an acute inhalation toxicity study is available. According to the data requirements as outlined in Annexes VII-VIII, 8.5 of Regulation (EC) 1907/2006 the choice for the second route of exposure shall depend on the likely route of human exposure. The inhalation route is considered as the major route of exposure.

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Acute oral toxicity

There is one reliable study for acute oral toxicity testing performed by Notox in 2010 according to the current valid EC guideline B.1 tris. The LD₅₀was determined to be > 2000 mg/kg bw. However, one impurity of strontium carbonate is barium carbonate with concentrations up to 2.5% (w/w). Barium carbonate is legally classified according to Directive 67/548/EEC Annex I as “Harmful if swallowed”. The generic cut-off value to consider for the purpose of classification is 1% for substances labelled “Acute tox. 4” (in accordance to regulation (EC) 1272/2008). Nevertheless, according to 3.1.3.6 of ECHA (2009) Guidance on the Application of Regulation (EC) 1272/2008, the ATE (Acute Toxicity Estimate) for strontium carbonate with 2.5 % (w/w) barium carbonate is above 2000 mg/kg bw. (for calculation please refer to section 5.2.3. of the CSR) and above the threshold value for classification as “Acute tox.4". The ATE_mixvalue using the formula above was calculated to be >12 000 mg/kg bw. Hence, no classification and labelling are required for strontium carbonate with 2.5 % (w/w) barium carbonate. Classification would only need to be considered if barium carbonate concentrations are above 15%.”

Specific target organ toxicant (STOT) – single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw in addition to this effects which were responsible for the death of the animals. No classification required.

 

Acute dermal toxicity

Following the HERAG guidance for metals and metal salts (see section 7.1.2 of the technical dossier, dermal absorption), a dermal absorption rate in the range of maximally 0.1-1.0 % can be anticipated. Dermal absorption in this order of magnitude is not considered to be “significant”.

In conclusion, testing for acute toxicity of strontium carbonate via the dermal route is not required according the criteria laid down in Annex VIII, point 8.5.

Thus, concerning dermal toxicity of strontium carbonate, following the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item shall not be classified as acutely toxic via the dermal route. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not to be classified.

 

Acute inhalation toxicity

Acute inhalation toxicity data or strontium carbonate are not available. However, for the following reasons, read across from strontium nitrate is considered feasible:

 

(i) acute inhalation toxicity of strontium nitrate: This study was performed with a maximum attainable concentration of 4.5 mg/L +- 0.6 mg/L strontium nitrate. Because of the extremely coarse nature of the test material (d50>300 µm), the investigators chose to formulate the test item in water, and to administer it via inhalation as an aqueous aerosol. In the study, only one out of ten animals died within the observation period (after 2 hours after start of exposure). The investigators conclude that the LC50 of strontium nitrate under these exposure conditions can safely be assumed to be > 5 mg/L. Considering the extremely coarse particle size of solid, crystalline strontium nitrate, then the LC₅₀ of solid strontium carbonate can also be assumed to be well above 5 mg/L.

 

(ii) relative bioavailability of strontium substances: strontium carbonate is poorly soluble in water (ca. 3 mg/L; pH ca. 7.5) whereas strontium nitrate is highly water soluble (ca. 667 g/L; pH ca. 6).  Thus, read-across from the soluble nitrate to the poorly soluble strontium carbonate is inherently conservative, since the factor 2,000-fold higher water solubility of the nitrate suggest a lower bioavailability of the carbonate.

 

(iii)  particle size considerations: whereas the “physical” particle size (d50 measured after dry dispersion by laser diffraction) indicates that strontium nitrate is much coarser than the two commercial grades of strontium carbonate, a more refined analysis involving cascade impactor particle size analysis of the airborne fraction in a rotating drum dustiness test with subsequent modelled deposition in the respiratory tract (see table below) demonstrates that under conditions of practical handling and use, all three materials show a similar deposition pattern to expected after inhalation exposure, with roughly similar inhalation absorption rates (ranging from 8.4-13.9%).

 

							deposition fractions			absorption factors		absorption factor via inhalation [%]
Sample	rel. Density	D50 [µm]	MMAD 1 [µm]	GSD 1	MMAD 2 [µm]	GSD 2	Head [%]	TB [%]	PU [%]	Head/TB (=GI) [%]	PU [%]
SrCO3(standard)	3.8 at 20°C	2.6	4.02 (35.7%)	1.82	34.2 (64.3%)	2.02	55.62	0.95	2.58	20.00	100.00	13.89
SrCO3(fine powder)	3.8 at 20°C	21.5	5.65 (3.0%)	2.63	32.77 (97.0%)	1.49	40.85	0.07	0.17	20.00	100.00	8.35
Sr(NO3)2	3.0 at 19°C	314.5	30.30	1.54	na	na	44.46	0.04	0.01	20.00	100.00	8.91

 

In conclusion, based on particle size and relative bioavailability considerations, read across from strontium nitrate to strontium carbonate is considered to be reasonable without restriction, and also to imply an inherent conservatism, so that the LC50 of strontium carbonate may reasonably be assumed to be > 5 mg/L. According to the regulation (EC) 1272/2008 the threshold value for LC₅₀ is > =5 mg/L. Hence, the test substance does not meet the criteria for classification and labelling according to GHS.

 

Specific target organ toxicant (STOT) – single exposure: inhalation

Laboured respiration was observed for two males between approximately 1.5 and 3.5 hours after start of exposure, including the male that was found dead.

Hunched posture, lethargy, rales, gasping, piloerection, chromodacryorrhoea and/or ptosis were observed among three males mainly between Days 1 and 6 after exposure. Rates were also observed during the second week of the observation period. No clinical signs were noted among the other animals. It can be concluded that these effect observed in two and three animals (out of ten), respectively are not sufficient for classification.