Registration Dossier

Administrative data

Description of key information

Data on repeated dose toxicity does not need to be provided due to exposure consideration. However, the substance decomposes under physiological conditions and releases fluorid which is assessed here in order not to oversee any relevant toxicological effects. Oral uptake amount leads to symptoms of fluoride poisoning if taken in considerable quantity (Marx 2006; Greyer 1975). Zinc metal was assessed by the Netherlands, findings published in EU Risk Assessment Report - Zinc metal. Zinc is an essential element and is regulated in the body (Cleven 1992), thus, no toxicity is expected by repeated intake of small dosis.

Hydrogen fluoride has been assessed by the Netherlands and the findings were published in the EU Risk Assessment Report - Hydrogen Fluoride. Although various data on animal studies, human studies and epidemiological data were assessed, the most reliable data were consider to be two inhalatory studies on rats. These were used to derive an NOAEL of 0.72 mg HF/m3.

The NOAEL of 0.72 mg/m3 derived in inhalatory studies with hydrogen fluoride in rats in not used to derive a DNEL. HF is absorbed very quickly by the body irrespective of exposure route. If fluoride is taken orally it is absorbed from the gastrointestinal tract quickly depending on amount of acid in the stomach. Uptake is slowed down by food, especially if calcium rich due to formation of inert calcium fluoride. Zinc hexafluorosilicate will decompose if getting in contact with water, e.g. moisture and does not directly form HF but rather a mixture of zinc cation, hydrated silica and fluoride. HF formation depends on the pH of water or solution the zinc hexafluorosilicate reacts with. Therefore, HF will not always form when zinc hexafluorosilicate decomposes but the worst-case approach is taken. The stated threshold of 1.5 mg/m3 is the SCOEL for hydrogen fluoride, 8 -hour TWA. Report "Recommendation from Scientific Committee on Occupational Exposure Limits for Fluorine, Hydrogen Fluoride and Inorganic Fluorides (not uranium hexafluoride)" is attached to this dossier and can be downloaded at https://www.ser.nl/documents/72888.pdf

The value is not corrected for stoichiometry as it would raise the threshold to 2.7 mg/m3.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Data waiving:
exposure considerations
Justification for data waiving:
a short-term toxicity study does not need to be conducted because relevant human exposure can be excluded as based on the provided thorough and rigorous exposure assessment
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
other: evidence based on degradation product
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes
Species:
rat
Sex:
male/female
Route of administration:
inhalation: gas
Dose / conc.:
0 mg/m³ air (analytical)
Dose / conc.:
0.098 mg/m³ air (analytical)
Dose / conc.:
0.72 mg/m³ air (analytical)
Dose / conc.:
7.52 mg/m³ air (analytical)
No. of animals per sex per dose:
20
Details on study design:
In a 91 days subchronic study (Placke and Griffin 1991), also performed according to GLP with similarity to OECD 413 guideline, female and male rats (20/group) were exposed to 0, 0.082, 0.816 and 8.16 mg HF/m3 (nominal concentrations; actual concentrations were: 0, 0.098, 0.72
and 7.52 mg/m3, respectively) for 6 hours/d, 5 days/week.
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Key result
Dose descriptor:
NOAEL
Effect level:
0.72 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
haematology
clinical biochemistry
organ weights and organ / body weight ratios
Conclusions:
From EU Risk Assessment Report on hydrogen fluoride:
The available animal data set for HF permits the derivation of a NOAEL for repeated sub- chronic inhalatory exposure. No suitable studies are available for HF, for other routes of exposure. The over-all NOAEL for repeated inhalatory exposure is taken from the 91-day GLP study with female and male rats and amounts 0.72 mg HF/m3 (actual value) for a 6 h per d 5 d per week exposure regimen. At this exposure no adverse effects were observed. At the next exposure level death, tissue irritation, dental malformations, haematological and biological changes and changes in several organ weights were observed.
Endpoint:
short-term repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
other: evidence from degradation product
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes
Species:
rat
Sex:
male/female
Route of administration:
inhalation: gas
Dose / conc.:
0 mg/m³ air (analytical)
Dose / conc.:
0.098 mg/m³ air (analytical)
Dose / conc.:
0.72 mg/m³ air (analytical)
Dose / conc.:
7.52 mg/m³ air (analytical)
No. of animals per sex per dose:
20
Details on study design:
In a 91 days subchronic study (Placke and Griffin 1991), also performed according to GLP with similarity to OECD 413 guideline, female and male rats (20/group) were exposed to 0, 0.082, 0.816 and 8.16 mg HF/m3 (nominal concentrations; actual concentrations were: 0, 0.098, 0.72
and 7.52 mg/m3, respectively) for 6 hours/d, 5 days/week.
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Key result
Dose descriptor:
NOAEL
Effect level:
0.72 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
haematology
clinical biochemistry
organ weights and organ / body weight ratios
Conclusions:
From EU Risk Assessment Report on hydrogen fluoride:
The available animal data set for HF permits the derivation of a NOAEL for repeated sub- chronic inhalatory exposure. No suitable studies are available for HF, for other routes of exposure. The over-all NOAEL for repeated inhalatory exposure is taken from the 91-day GLP study with female and male rats and amounts 0.72 mg HF/m3 (actual value) for a 6 h per d 5 d per week exposure regimen. At this exposure no adverse effects were observed. At the next exposure level death, tissue irritation, dental malformations, haematological and biological changes and changes in several organ weights were observed.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
0.72 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The parent inorganic hexafluorosilicates salts are not harmonised classified with repeated dose toxicity. No classification for zinc hexafluorosilicate is proposed because of lack of relevant data indicating repeated dose toxicity.