Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.8 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:
2.7 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.8 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:
0.37 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.38 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Read-across justification

 

Introduction:

Reliable substance-specific information concerning the toxicity for zinc difluoride does not exist. Instead, toxicological information on very soluble inorganic fluoride (mainly sodium fluoride) substances and very soluble inorganic zinc substances were extrapolated to zinc difluoride considering that systemic effects mainly based on the concentrations of the Zn2+ and F- ions, which are the key concern of zinc difluoride.

Zinc difluoride – general considerations

 

Zinc difluoride (tetrahydrate) completely dissolves upon contact and during the reaction with water to Zn2+and 2*F-. The water solubility (CRC handbook, 2008) of zinc difluoride tetrahydrate indicates a high dissolution and a rapid formation of Zn2+and 2*F-(15.5 g/L at 25°C; logK 3.34). The pH value of a 5% aqueous solution of zinc difluoride tetrahydrate is pH 4.9. Considering that human health effects of zinc difluoride mainly based on the concentration of Zn2+and F-in solution, read-across to very soluble (i.e., > 10 g/L at room temperature) inorganic zinc compounds and very soluble (i.e., > 10 g/L at room temperature) inorganic fluoride compounds are performed.

 

Fluoride:

Zinc difluoride and zinc difluoride tetrahydrate, respectively which is manufacture and marked, belongs to the soluble inorganic substances based on the water solubility of 15.5 g/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. 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 CSR chapter on repeated dose toxicity and the resulting derivation of DNELs.

Read-across: particularly in animal studies, the most common inorganic fluoride salt sodium fluoride is used as test item. Other soluble salts of fluoride, such as potassium fluoride, ammonium fluoride or also potassium hydrogen difluoride are also used occasionally. Unrestricted read-across is possible between these substances with regards to systemic toxicity, which is of key concern for fluorides. All mentioned fluorides are readily soluble (water solubilities of several tens or hundreds of grams per litre) and release the fluoride ion 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 IULCID section 5.1.2 "Hydrolysis- ZnF2_Hägg Graph - Fluorides".

 

Zinc:

Zinc 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 zinc cation in both animals and in humans is an important determinant of toxicity, and although there is information available on the various zinc compounds, adequate information is lacking on how to quantitatively determine or estimate the bioavailable fraction of all the different zinc compounds in either laboratory animals or humans (Windholzet al., 1983). Since water solubility is the main determinant of bioavailability, zinc compounds with similar solubility characteristics have been grouped and, where necessary, the local or systemic toxicity have been read-across within the same group of zinc compounds.

In sum, data are read-across for soluble inorganic zinc substances and for different fluoride salts (mainly sodium fluoride) to assess the toxicity of zinc difluoride (tetrahydrate) on a conservatively basis in view of the water solubility. All read-across substances used for the assessment of zinc difluoride are more soluble (≥ 41 g/L) than zinc difluoride tetrahydrate (15.5 g/L). Since, the toxicity of zinc and fluoride is based on the concentration of cation and ion in solution read-across is considered to be worst-case and unrestricted read-across is fully justified with regard to systemic toxicity, which is the key concern of zinc difluoride.

For more detailed information please refer to the document attached on IUCLID section 0 “categories”.

General Population - Hazard via inhalation 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
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