Registration Dossier

Administrative data

Description of key information

Reliable substance-specific data on acute oral toxicity for tin difluoride do not exist. However, based on the reported acute oral LD50 values for the read-across substance sodium fluoride in experimental animals and the assumption that the fluoride anion is determinant for acute oral toxicity (demonstrated by a comparison with the results of other Sn(II) substances), the acute oral toxicity can be extrapolated to tin difluoride, yielding a classification as acute toxic 3 if ingested.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
After dissolution and disociation in environmental (aqueous)/physiolological media the constituents of tin difluoride become bioavailable and the overall toxicity of the dissociated substance can be described by the toxicity of the individual constituents/ions. Since synergistic effects are not to be expected, the human health and environmental hazard assessment of the assessment entity tin difluoride consists of an individual assessment of the assessment entities tin cation and the fluoride anion. The tin cation and the fluoride anion are considered to represent the overall toxicity of tin difluoride in a manner proportionate to the fluoride and the metal (represented by one of its readily soluble salts). Based on the above information, unrestricted read-across is considered feasible and justified.
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
- a control group was not included.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Portage, MI, USA
- Weight at study initiation: 190 - 300 g (fasted weight)
- Fasting period before study: No data

ENVIRONMENTAL CONDITIONS
- Followed approved Standard Operating Procedures of the test facility


Route of administration:
oral: gavage
Vehicle:
other: deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4.0% w/v in deionized water
- Amount of test substance and vehicle dosed (if gavage): 2.86, 3.4, 4.0 or 5.6 mL/kg body weight
- Justification for choice of vehicle: test substance was readily soluble up to 4% in water


Doses:
Dose levels evaluated were: 114, 136, 160 and 224 mg NaF/kg body weight.
No. of animals per sex per dose:
10 female rats per dose
Control animals:
no
Details on study design:
After a single oral gavage dose, all animals were observed for mortality at frequent intervals during the first 4 hours after dosing (at least once during the first 30 minutes) and daily thereafter for the next 14 days.
Statistics:
The LD50 value and 95% confidence limits were calculated by the Probit Method [ J. Finney, Probit Analysis, 3rd Ed., Cambridge Univ. Press, 1971, pp. 50-90] by use of the computer program BLISS17 [Fortran version of BLISS17 program, written by D.J. Finney].
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 148.5 mg/kg bw
95% CL:
>= 116.3 - <= 185.5
Mortality:
Dose Level Number of Deaths
114 mg/kg 2/10
136 mg/kg 4/10
160 mg/kg 7/10
224 mg/kg 8/10
336 mg/kg 8/8
500 mg/kg 8/8
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
LD50 (female rats): 148.5 mg/kg bw (95% confidence limits of 116.3 - 185.5 mg/kg bw)
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is acutely toxic via the oral route (Category 3).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
148.5 mg/kg bw

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study conducted by GLP accredited lab using OECD guideline method 402
Justification for type of information:
After dissolution and disociation in environmental (aqueous)/physiolological media the constituents of tin difluoride become bioavailable and the overall toxicity of the dissociated substance can be described by the toxicity of the individual constituents/ions. Since synergistic effects are not to be expected, the human health and environmental hazard assessment of the assessment entity tin difluoride consists of an individual assessment of the assessment entities tin cation and the fluoride anion. The tin cation and the fluoride anion are considered to represent the overall toxicity of tin difluoride in a manner proportionate to the fluoride and the metal (represented by one of its readily soluble salts). Based on the above information, unrestricted read-across is considered feasible and justified.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
other: skin was wetted, but the kind of vehicle was not stated
Details on dermal exposure:
not specified
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured
Clinical signs:
Pitting and eschar formation at the application site.
A second study at 1000 mg/kg showed pitting, erythem, echar formation and desquamation at the application site
Body weight:
Male animals showed expected body weight gains, but all females showed lower gains than expected.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (male and female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the dermal route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Read-across:

No reliable substance specific information concerning acute oral toxicity for tin difluoride exist to date. Thus, it is considered appropriate to use toxicological information for the anion from read-across to soluble fluoride substances such as sodium- and potassium fluoride. The contribution of sodium and potassium cations to the toxicity of these substances is considered to be negligible, also in view of their physiological relevance.

In key acute oral toxicity studies (Proctor & Gamble, 1984, 1985), the LD50 for sodium fluoride in male Sprague-Dawley rats was reported to be 223 mg/kg body weight with 95% confidence limits of 177 - 272 mg/kg body weight, and the LD50 for sodium fluoride in female Sprague-Dawley rats was reported to be 148.5 mg/kg body weight with 95% confidence limits of 116.3 - 185.5 mg/kg body weight, respectively. Taking into account the most sensitive species (female), a stoichiometric recalculation to tin difluoride yields an LD50 value of approx. 280 mg/kg.

By comparison, acute oral toxicity data for SnCl2 (Conine, 1975) rated as reliable provide an LD50 value for Sn(II) of about 1207 mg/kg, indicating a much lower class of toxicity than the fluoride anions. Hence, the data for the fluoride anion were taken as the basis for classification purposes.

Justification for classification or non-classification

According to EU classification, labelling and packaging of substances and mixtures (CLP) regulations (EC no 1272/2008), tin difluoride should be classified as acute toxic class 3 for acute oral toxicity.