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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.47 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.47 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Read-across justification

 

Introduction:

Reliable substance-specific information concerning the toxicity for strontium difluoride does not exist. Instead, toxicological information on very soluble inorganic fluoride (mainly sodium fluoride) substances and very soluble inorganic strontium substances were extrapolated to strontium difluoride considering that systemic effects mainly based on the concentrations of the Sr2+ and F- ions, which are the key concern of strontium difluoride.

Strontium difluoride – general considerations

Strontium difluoride completely dissolves upon contact with water to Sr2+and 2*F-. The water solubility (CRC handbook, 2008) of strontium difluoride indicates a complete dissolution and a rapid formation of Sr2+and 2*F-(210 mg/L at 25°C; logK 8.4). The pH of a saturated aqueous solution of strontium difluoride is pH 4.9. Considering that systemic human health effects of strontium difluoride are due the dissolved concentrations of Sr2+and F-in physiological solutions, read-across to very soluble (i.e., > 10 g/L at room temperature) inorganic strontium compounds and very soluble (i.e., > 10 g/L at room temperature) inorganic fluoride compounds is performedand considered to be very conservative.

 

In sum, data are read-across for soluble inorganic strontium substances and for different fluoride salts (mainly sodium fluoride) and avid to assess the toxicity of strontium difluoride on a conservatively basis in view of the water solubility. All read-across substances used for the assessment of strontium difluoride are more soluble (≥ 41 g/L) than strontium difluoride (210 mg/L at 25°C).Since, the toxicity of strontium difluoride is based on the concentration of strontium cations and fluoride anions in solution, read-across is considered to be conservative and unrestricted read-across is fully justified with regard to systemic toxicity.

 

Strontium(II):

Strontium ions are highly mobile, occur only in one valence state (2+), i.e. are not oxidized or reduced, and do not form strong complexes with most inorganic and organic ligands (Krupka et al. 1999. EPA 402-R-99-004B; Salminen et al. 2005; Carbonaro and Di Toro. 2007. Geochim Cosmochim Acta 71 3958–3968; Carbonaro et al. 2011. Geochim Cosmochim Acta 75: 2499-2511 and references therein). Thus, it may be assumed that systemic toxicological effects (not local) are related to the strontium ion.

 

Strontium exists in different chemical forms and the bioavailability of these forms depends on various physico-chemical parameters of which water solubility is the main determining factor. It is accepted that the actual bioavailable concentration of the strontium cation in both animals and in humans is an important determinant of toxicity, and although there is information available on the various strontium compounds, adequate information is lacking on how to quantitatively determine or estimate the bioavailable fraction of different strontium compounds in laboratory animals or humans. Since water solubility is the main determinant of bioavailability, strontium compounds with similar solubility characteristics are grouped and the systemic toxicity is read-across withinthe category “soluble inorganic strontium substances”.The respective counter-ions are not assumed to contribute significantly to any toxicity.

 

Fluoride:

Strontium difluoride belongs to the moderately soluble inorganic substances based on the water solubility of 210 mg/L at 25°C (CRC, 2008).It is common practice in the scientific and regulatory community to assess the physiological function and the toxicity of inorganic fluorides in general.This read-across approach was already applied in the EU Risk Assessment of hydrogen fluoride (2001) as follows: “Absorption of any inorganic fluoride is thought to be a passive process. Inorganic fluoride of any source is thought to be transported across biological membranes primarily as molecular (non-ionic thus uncharged) HF. At physiological pH (in blood, intercellular fluid, mucus) free fluoride (thus not associated with e.g. proteins or lipids) exists primarily as fluoride ion (F-); only 0.01% of the total free fluoride concentration exists as molecular HF in equilibrium with the ionic form (Anonymus 1996). The fate or effects of absorbed inorganic fluoride are independent of the fluoride source (Thiessen 1988)”.

 

Several national and international bodies have assessed fluoride in the past, for example the US DHHS (1991), SCOEL (1998), WHO (2002), MAK (2006 with update 2007), EFSA (2006). The two most recent reviews by MAK (focussed on worker exposure via inhalation) and EFSA (focussed on oral exposure for the general population) have been considered extensively in the preparation of the IUCLID chapter on human health toxicity and the resulting derivation of DNELs.

 

In animal studies, the most common inorganic fluoride salt, i.e. sodium fluoride, has been tested. Other soluble salts of fluoride, such as potassium fluoride, ammonium fluoride or also potassium hydrogen difluoride were tested in a few studies. Unrestricted read-across is possible between these substances with regards to systemic toxicity of fluoride. All fluoride substances grouped into the category “soluble inorganic fluoride substancs” are readily soluble (water solubilities of several tens or hundreds of grams per litre) and release fluoride ions F-.

 

The respective counter-ions are not assumed to contribute significantly to any toxicity. A Hägg-Diagram (1983) shows the speciation (as molar fractions) of the HF/F- system. Under neutral, physiologically relevant conditions, F- is the only relevant species.The Hägg-Diagram is attached on IUCLID section 5.1.2 Hydolysis "SrF2_Hägg Graph - Fluorides".

Therefore, the assessment of the systemic toxicity of strontium difluoride is based on elemental strontium and fluoride concentrations. Read-across of systemic (not local) effects data available for soluble strontium substances and soluble fluoride substances is applied since the strontium ions and fluoride ions determine the systemic toxicity potential of strontium difluoride.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:
In accordance with ECHA guidance on information requirements and chemical safety assessment, Part: E: risk characterisation, version 3.0, May 2016: "DNELs for the general population may need to be derived if the substance is present in consumer - available products or is released to the environment and present as an environmental contaminant."
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population