Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
1 736 mg/kg bw
Quality of whole database:
study conducted with strontium nitrate, results re-calculated to strontium sulfate

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
3 900 mg/m³
Quality of whole database:
study conducted with strontium nitrate, results re-calculated to strontium sulfate

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Toxicological relevance of the counterion “sulfate”

The registrant is of the opinion that the toxicity of strontium sulfate is driven by the strontium moiety and that the sulfate anion does not contribute to the overall toxicity of the substance strontium sulfate to any relevant extent, for the following reasons:

Sulfate anions are abundantly present in the human body in which they play an important role for the ionic balance in body fluids. Sulfate is required for the biosynthesis of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) which in turn is needed for the biosynthesis of many important sulfur-containing compounds, such as chondroitin sulfate and cerebroside sulfate. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) concludes that the few available studies in experimental animals do not raise any concern about the toxicity of the sulphate ion in sodium sulphate. Sodium sulphate is also used clinically as a laxative. In clinical trials in humans using 2-4 single oral doses of up to 4500 mg sodium sulphate decahydrate per person (9000 – 18000 mg per person), only occasional loose stools were reported. These doses correspond to 2700 - 5400 mg sulphate ion per person. High bolus dose intake of sulphate ion may lead to gastrointestinal discomfort in some individuals. No further adverse effects were reported (JECFA 2000, 2002). This position was adopted by the European Food Safety Authority (EFSA 2004) without alteration.

Based on the above information, one can therefore safely assume that the sulfate anion in strontium sulfate does not contribute to the overall toxicity of strontium, sulfate. It is concluded that only the effect of “strontium” is further considered in the human health hazard assessment of strontium sulfate.

Read across from Sr(NO3)2 to SrSO4:

The toxicity of strontium substances such as strontium sulfate can reasonably assumed to be determined by the availability of strontium ions in solution. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Strontium nitrate is highly water soluble with ≤ 802 g/L at pH ~ 7, whereas strontium sulfate is moderately soluble (~125 mg/L at pH ~ 6.5). Hence, any read across from strontium nitrate to strontium sulfate is inherently very conservative.

 

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. The LD50was determined to be > 2000 mg Sr(NO3)2/kg bw. Re-calculation the value to strontium sulfate results in an unbounded value of 1,736 mg SrSO4/kg bw. One out of six animals was found dead within 4 hours post-treatement on Day 1. According to the Regulation (EC) 1272/2008 the threshold value for LD50is > =2000 mg/kg bw. However, since read across from strontium nitrate to strontium sulfate is fully justified (see discussion) but very conservative, it may be concluded that the LD50of strontium sulfate is > 2000 mg/kg bw.

Furthermore, as stated by SIDS, 2007 there is an acute oral toxicity study (OECD TG 423) available, initiated by the national institute of environmental research (NIER), Korea in 2006. In this study a dose of2,000 mg/kg bw of strontium sulfate were administered orally to three femaleSprague-Dawley(Crl:CD) rats. No mortality and toxic signs in any of the animals were observed. All rats showed consistent body weight gain at the end of the observation period. Gross pathology on animals revealed no abnormality.Hence, the LD50results in an unbounded value of > 2,000 mg SrSO4/kg bw. Despite extensive effort, the original study could not be made available.

Reference:Anonymous (2007) SIDS, initial assessment report for SIAM 24, Paris, France, 17 -20 April 2007

 

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 sulfate via the dermal route is not required according the criteria laid down in Annex VIII, point 8.5.

However, as stated in SIDS, 2007 anacute dermal toxicity study with strontium sulfate was initiated under OECD TG 402 in compliance with GLPby the national institute of environmental research (NIER), Korea in 2006.Aqueous solution of strontium sulfate was applied in a volume of 3 mL/kg bw to the skin of 8-week old Sprague-Dawley rats (5 animals/sex/group) at dose of 0 and 2,000 mg/kg bw. The animals were observed for 14 days following a single treatment. No mortality and clinical signs occurred and no macroscopic change was observed in any animals at autopsy.

Reference:Anonymous (2007) SIDS, initial assessment report for SIAM 24, Paris, France, 17 -20 April 2007

 

Acute inhalation toxicity

There is one study on acute toxicity, inhalation available. This study was performed with a limit concentration of 4.5 mg/L +- 0.6 mg/L strontium nitrate. Re-calculating this value to strontium sulfate, results in an unbounded value of 3.9 mg SrSO4/L +-0.5 mg/L. One out of ten animals died within the observation period (after 2 hours after start of exposure). According to the regulation (EC) 1272/2008 the threshold value for LC50is > =5 mg/L. However, since read across from strontium nitrate to strontium sulfate is fully justified (see discussion) but very conservative, it may be concluded that the LC50of strontium sulfate is > 5 mg/L.


Justification for selection of acute toxicity – oral endpoint
reliable GLP guideline study available

Justification for selection of acute toxicity – inhalation endpoint
reliable GLP guideline study available

Justification for selection of acute toxicity – dermal endpoint
Acute dermal toxicity study does not need to be performed since an acute inhalation toxicity study is available which is considered to be the major route of exposure for this substance. 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. Furthermore, 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”.

Justification for classification or non-classification

Acute toxicity

Based on the available data on acute toxicity data for strontium sulfate and other strontium substances it is concluded that no classification and labelling is required in accordance with Regulation (EC) No 1272/2008 and subsequent regulations for acute toxicity (oral, dermal and inhalation).

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.

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.