Registration Dossier

Administrative data

Description of key information

The oral LD50 for male rats was 2.72 (2.52-2.93) g/kg bw, the oral LD50 for female rats was 2.15 (1.61-2.89) g/kg bw.
The rat inhalation LC50 for 1 hour was >4.92 mg/L.
The dermal LD50 value was >2.0 g/kg bw in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, some restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Five male and five female animals were used for each of 5 oral dosage levels and held for a 14-day observation period
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Sample number: 41105731
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Madison WI
- Age at study initiation: 7 weeks
- Weight at study initiation: 202-300 g
- Fasting period before study: overnight
- Housing: 5/cage
- Diet: ad libitum, Purina Rodent Chow
- Water: ad libitum
- Acclimation period: 7 days
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10.0 ml/kg bw
Doses:
Males: 2.55, 2.75, 3.00, 3.57, 5.00 g/kg
Females: 1.30, 1.82, 2.55, 3.57, 5.00 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality: 1, 2.5 and 4 hrs after administration and daily thereafter. Weighing: before administration and on day 7 and 14
- Gross necropsy of animals which died: yes
- Gross necropsy of survivors performed: no
Statistics:
Thakur, A.K., and Fezio, W.L., 1891. A computer program for estimating LD50 and its confidence limits using a modified Behrens-Reed-Muench cumulant method. Drug and Chemical Toxicology, 297-305.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 2.72 other: g/kg bw
95% CL:
2.52 - 2.93
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2.15 other: g/kg bw
95% CL:
1.61 - 2.89
Mortality:
Males: 2.55 g/kg: 0/5 (0 of 5 animals); 2.75 g/kg: 3/5; 3.57-5.00 g/kg: 5/5
Females: 1.30 g/kg: 0/5; 1.82 g/kg: 2/5; 2.55 g/kg: 3/5; 3.57-5.00 g/kg: 5/5
Clinical signs:
not reported
Body weight:
no differences in body weight observed between dosage levels
Gross pathology:
In the animals which died histopathological lesions were observed mainly in the gastro-intestinal tract, primarily in the stomach.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, some restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Five male and five female animals were used for 3 and 4 oral dosage levels, respectively, and held for a 14-day observation period
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Madison WI
- Age at study initiation: 7 weeks
- Weight at study initiation: 210-286 g
- Fasting period before study: overnight
- Housing: 5/cage
- Diet: ad libitum, Purina Rodent Chow
- Water: ad libitum
- Acclimation period: 7 days
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10.0 ml/kg bw
Doses:
Males: 3.57, 5.00, 7.00 g/kg
Females: 2.55, 3.57, 4.25, 5.00 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality: 1, 2.5 and 4 hrs after administration and daily thereafter. Weighing: before administration and on day 7 and 14
- Gross necropsy of animals which died: yes
- Gross necropsy of survivors performed: no
Statistics:
Thakur, A.K., and Fezio, W.L., 1891. A computer program for estimating LD50 and its confidence limits using a modified Behrens-Reed-Muench cumulant method. Drug and Chemical Toxicology, 297-305.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 4.73 other: g/kg bw
95% CL:
3.66 - 6.11
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 4.13 other: g/kg bw
95% CL:
3.58 - 4.75
Mortality:
Males: 3.57 g/kg: 0/5; 5.00 g/kg: 3/5; 7.00 g/kg: 5/5
Females: 2.55 g/kg: 0/5; 3.57 g/kg: 0/5; 4.25 g/kg: 3/5; 5.00 g/kg: 5/5
Clinical signs:
not reported
Body weight:
no differences in body weight observed between dosage levels
Gross pathology:
In the animals which died histopathological lesions were observed mainly in the gastro-intestinal tract, primarily in the stomach.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, some restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Five male and five female animals were used for 3 and 5 oral dosage levels, respectively, and held for a 14-day observation period
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Madison WI
- Age at study initiation: 7 weeks
- Weight at study initiation: 200-299 g
- Fasting period before study: overnight
- Housing: 5/cage
- Diet: ad libitum, Purina Rodent Chow
- Water: ad libitum
- Acclimation period: 7 days
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10.0 ml/kg bw
Doses:
Males: 3.57, 5.00, 7.00 g/kg
Females: 2.55, 2.57, 3.00, 3.57, 5.00 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality: 1, 2.5 and 4 hrs after administration and daily thereafter. Weighing: before administration and on day 7 and 14
- Gross necropsy of animals which died: yes
- Gross necropsy of survivors performed: no
Statistics:
Thakur, A.K., and Fezio, W.L., 1891. A computer program for estimating LD50 and its confidence limits using a modified Behrens-Reed-Muench cumulant method. Drug and Chemical Toxicology, 297-305.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 4.49 other: g/kg bw
95% CL:
3.44 - 5.87
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2.72 other: g/kg bw
95% CL:
2.52 - 2.93
Mortality:
Males: 3.57 g/kg: 1/5 (1 of 5 animals); 5.00 g/kg: 3/5; 7.00 g/kg: 5/5
Females: 2.55 g/kg: 0/5; 2.75 g/kg: 3/5; 3.00 g/kg: 5/5; 3.57 g/kg: 5/5; 5.00 g/kg: 5/5
Clinical signs:
not reported
Body weight:
no differences in body weight observed between dosage levels
Gross pathology:
In the animals which died histopathological lesions were observed mainly in the gastro-intestinal tract, primarily in the stomach.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 150 mg/kg bw
Quality of whole database:
Studies performed in accordance with standard guidelines.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, non-guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
One group of 5 male and 5 female rats was exposed to 4.92 mg/L of the test substance for 1 hour, followed by an observation period of 14 days.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Sample number: 41105734
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl:CD (SD) BR
- Source: Charles River Breeding Laboratories, Portage, MI.
- Weight at study initiation: Mean of 233 g (males) and 225 g (females).
- Fasting before study: none
- Housing: individually, cage size conformed to the standards specified in DHEW Publication (NIH) 78.23
- Diet: ad libitum, Purina Certified Rodent Chow 5002, ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): within the range specified in ABC SOP's
- Humidity (%): within the range specified in ABC SOP's
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
1.3 µm
Geometric standard deviation (GSD):
1.58
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass inhalation chamber
- Exposure chamber volume: 80
- Method of holding animals in test chamber: cage
- Source and rate of air: 21.1 l/min
- System of generating particulates/aerosols: The aerosol was generated by passing a stream of air through the test article contained in a dust shaker mechanism. The resulting air-dust mixture entered the top center of the inhalation chamber and exhausted at the bottom of the chamber. A stream of additional air was added to the chamber to achieve the desired concentration and to aid in test article dispersion
- Method of particle size determination: Delron cascade impactor, model no. DCI-6
- Treatment of exhaust air: Exhausted test atmosphere was diluted prior to release to the outside atmoshpere via an exhaust blower
- Temperature, humidity, pressure in air chamber: T: 72.3 F; RH: 40.0%; P: -0.10 inches of water

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrical analysis
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: 99.8% of the weight of the particles is contributed by particles less than or equal to 10.0 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 1.30 µm / GSD: 1.58
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrical analysis
Duration of exposure:
1 h
Concentrations:
4.92 mg/L (gravimetric concentration); 87.2 mg/L (nominal concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During exposure: incidence of mortality and reactions displayed every 15 min. Observation period: twice daily mortality checks. Weighing: prior to exposure and on day 14
- Gross necropsy of survivors performed: yes, external surface and body orifices, cervical organs, thoracic organs, abdominal and pelvic organs, and the brain
Preliminary study:
not performed
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.92 mg/L air
Exp. duration:
1 h
Mortality:
Four ot the test animals died during the study (1 male, 3 females)
Clinical signs:
other: Irregular breathing, poor coat quality, yellow/brown stained fur, lethargy, crusty eye, crusty nose, and crusty muzzle
Body weight:
The surviving animals exhibited body weight gains during the invenstigational period.
- Males: Day 0: 233.4 g (SD15.9), Day 14: 281.0 g (SD 28.1).
- Females: Day 0 225.0 g (SD 24.9), Day 14: 245.5 g (SD 30.4)
Gross pathology:
Abnormalities of the stomach (multifocal erosions, diffuse red brown discoloration of glandular mucosa), glandular stomach (mucosa smooth and discolored red brown), heart (diffusely pale, tan discoloration, mottling) and small intestine (dark contents) were observed in 2 males and 3 females.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The inhalatory LC50, 4h value of multiconsituent aluminium potassium fluoride in rats was established to be within the range of 1 – 5 mg/L.
Executive summary:

The acute inhalation toxicity of multiconsituent aluminium potassium fluoride in the rat was investigated in a GLP compliant, non-guideline study. Despite some minor restrictions in design and/or reporting, the study is considered as adequate for assessment.

One group of 5 male and 5 female rats was exposed whole body to a dust atmosphere of the test substance. The duration of the exposure was 1 hour followed by a 14 day observation period. The gravimetric concentration of test article in the test atmosphere was 4.92 mg/l. Particle size analysis of the exposure chamber revealed a mass median diameter of 1.30 µm and geometric standard deviation of 1.58.

Four of the test animals died during the study. Irregular breathing, poor coat quality, yellow/brown stained fur, lethargy, crusty eye, crusty nose, and crusty muzzle were observed among the test animals during the study period. Necropsies revealed no gross lesions in 5 of 10 test animals. Abnormalities of the small intestine, stomach, and heart were observed in the remaining test rats. Based on the observed mortality it can be concluded that the 1-hour LC40 of the test substance is 4.92 mg/L which would correspond to a 4-hour LC40 of 1.23 mg/l when applying Haber's rule. The 4 -hour LC50 will be slightly above this concentration.

Based on the above observations, the inhalatory LC50, 4h value of multconstituent aluminium potassium fluoride in rats was established to be within the range of 1 – 5 mg/L and therefore the test substance needs to be classified as Category 4 H332 'Harmful if inhaled' according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, non-guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
One group of 5 male and 5 female rats was exposed to 3.4 mg/L of the test substance for 1 hour, followed by an observation period of 14 days.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CrL:CD( SD) BR
- Source: Charles River Breeding Laboratories, Portage, MI
- Weight at study initiation: males: 282-298 g; females: 212-228 g
- Housing: individually, cage size conformed to the standards specified in DHEW Publication (NIH) 78.23
- Diet: ad libitum, Purina Cerified Rodent Chow 5002, ad libitum
- Water: ad libitum, filtered tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): within the range specified in ABC SOP's
- Humidity (%): within the range specified in ABC SOP's
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass inhalation chamber
- Exposure chamber volume: 80
- Method of holding animals in test chamber: cage
- Source and rate of air: 21.1 l/min
- System of generating particulates/aerosols: The aerosol was generated by passing a stream of air through the test article contained in a dust shaker mechanism. The resulting air-dust mixture entered the top center of the inhalation chamber and was exhausted at the bottom of the chamber. A stream of additional air was added to the chamber to achieve the desired concentration and to aid in test article dispersion
- Method of particle size determination: Delron cascade impactor, model no. DCI-6
- Treatment of exhaust air: Exhausted test atmosphere was diluted prior to release to the outside atmoshpere via an exhaust blower
- Temperature, humidity, pressure in air chamber: T: 74.7 F; RH: 40.0%; P: -0.10 inches of water

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrical analysis
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: 99.8% of the weight of the particles is contributed by particles less than or equal to 10.0 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 1.77 µm / GSD: 1.84
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrical analysis
Duration of exposure:
1 h
Concentrations:
3.38 mg/l (gravimetrical time-weighted average); 48.2 mg/l (nominal concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During exposure: incidence of mortality and reactions displayed every 15 min. Observation period: twice daily mortality checks, observations: once daily. Weighing: prior to exposure and on days 7 and 14
- Necropsy of survivors performed: yes, external surface and body orifices, cervical organs, thoracic organs, abdominal and pelvic organs, and the brain
Preliminary study:
not performed
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.4 mg/L air
Exp. duration:
1 h
Mortality:
1 female
Clinical signs:
other: Irregular breathing, ataxia, lethargy, and crusty nose
Body weight:
Mean (+/- SD) in grams. Males: day 0: 289.6 (7.5), day 7: 303.6 (11.1), day 14: 333.0 (9.7). Females: day 0 219.2 (5.9), day 7: 226.8 (9.4), day 14: 241.5 (14.5)
Gross pathology:
No abnormalities in the survivors.
Abnormalities of the heart and stomach were observed in the female that died during the study.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
GLP study according to standard guidelines.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Five male and five female rabbits were used for a single dermal dosage level of 2.0 g/kg bw and held for an observation period of 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Sample number: 41105731
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: 14 weeks
- Weight at study initiation: 2497 - 2891 g
- Housing: screen-bottom cages, individually
- Diet: ad libitum, Teklad Laboratory Rabbit diet
- Water: ad libitum
- Acclimation period: at least 7 days
Type of coverage:
occlusive
Vehicle:
other: test material is moistened with 0.9% saline
Details on dermal exposure:
TEST SITE
- Area of exposure: animals' shaved back
- % coverage: shaved area made up approximately 20% of the total body surface
- Type of wrap if used: 4x4-inch gauze patch secured with paper tape and overwrapped with Saran Wrap and Elastoplast tape.
- Just before the test material was applied, longitudinal epidermal abrasions (deep enough to penetrate the stratum corneum, not deep enough to penetrate to the dermal layer and cause bleeding) were made on the exposed back of two male and three female animals.

REMOVAL OF TEST SUBSTANCE
- Backs were wiped clean with wet disposable paper towels.
- Time after start of exposure: 24 hrs
Duration of exposure:
single dose for 24 hrs
Doses:
2.0 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations (dermal irritation, clinical signs and mortality): daily; weighing: just prior to test material application and on day 7 and 14
- Necropsy of survivors performed: no
Statistics:
not reported
Preliminary study:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 other: g/kg bw
Mortality:
no mortality
Clinical signs:
no clinical signs are reported
Body weight:
no differences in body weight observed between dosage levels
Gross pathology:
not reported
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Five male and five female rabbits were used for a single dermal dosage level of 2.0 g/kg bw and held for an observation period of 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: 14 weeks
- Weight at study initiation: 2410 - 2722 g
- Housing: screen-bottom cages, individually
- Diet: ad libitum, Teklad Laboratory Rabbit diet
- Water: ad libitum
- Acclimation period: at least 7 days
Type of coverage:
occlusive
Vehicle:
other: test material is moistened with 0.9% saline
Details on dermal exposure:
TEST SITE
- Area of exposure: animals' shaved back
- % coverage: shaved area made up approximately 20% of the total body surface
- Type of wrap if used: 4x4-inch gauze patch secured with paper tape and overwrapped with Saran Wrap and Elastoplast tape.
- Just before the test material was applied, longitudinal epidermal abrasions (deep enough to penetrate the stratum corneum, not deep enough to penetrate to the dermal layer and cause bleeding) were made on the exposed back of two male and three female animals.

REMOVAL OF TEST SUBSTANCE
- Backs were wiped clean with wet disposable paper towels.
- Time after start of exposure: 24 hrs
Duration of exposure:
single dose for 24 hrs
Doses:
2.0 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations (dermal irritation, clinical signs and mortality): daily; weighing: just prior to test material application and on day 7 and 14
- Necropsy of survivors performed: no
Statistics:
not reported
Preliminary study:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 other: g/kg bw
Mortality:
no mortality
Clinical signs:
no clinical signs are reported
Body weight:
no differences in body weight observed between dosage levels
Gross pathology:
not reported
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Five male and five female rabbits were used for a single dermal dosage level of 2.0 g/kg bw and held for an observation period of 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: 14 weeks
- Weight at study initiation: 2392 - 2832 g
- Housing: screen-bottom cages, individually
- Diet: ad libitum, Teklad Laboratory Rabbit diet
- Water: ad libitum
- Acclimation period: at least 7 days
Type of coverage:
occlusive
Vehicle:
other: test material is moistened with 0.9% saline
Details on dermal exposure:
TEST SITE
- Area of exposure: animals' shaved back
- % coverage: shaved area made up approximately 20% of the total body surface
- Type of wrap if used: 4x4-inch gauze patch secured with paper tape and overwrapped with Saran Wrap and Elastoplast tape.
- Just before the test material was applied, longitudinal epidermal abrasions (deep enough to penetrate the stratum corneum, not deep enough to penetrate to the dermal layer and cause bleeding) were made on the exposed back of two male and three female animals.

REMOVAL OF TEST SUBSTANCE
- Backs were wiped clean with wet disposable paper towels.
- Time after start of exposure: 24 hrs
Duration of exposure:
single dose for 24 hrs
Doses:
2.0 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Treatment: just before the test material was applied, longitudinal epidermal abrasions were made on the exposed backs of two male and three female rabbits. The abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to penetrate to the dermal layer and cause bleeding.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations (dermal irritation, clinical signs and mortality): daily; weighing: just prior to test material application and on day 7 and 14
- Necropsy of survivors performed: no
Statistics:
not reported
Preliminary study:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 other: g/kg bw
Mortality:
no mortality
Clinical signs:
no clinical signs are reported
Body weight:
no differences in body weight observed between dosage levels
Gross pathology:
not reported
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
Studies performed in accordance with standard guidelines.

Additional information

Oral route

Three acute oral toxicity studies equivalent or similar to OECD guideline 401 are available (Hazleton Laboratories, 1985a,b,c). Different multiconstituent aluminium potassium fluoride batches were tested: aluminium potassium fluoride 100 FLUX (AT-1 -KC), aluminium potassium fluoride NK FLUX (AT-2-NK) and aluminium potassium fluoride NK FLUX (AT-3-NL). Different dose levels were tested in the studies. The following results were observed regarding mortality:

 

Aluminium potassium fluoride 100 FLUX (AT-1-KC):

Males: 2.55 g/kg: 0/5 (0 of 5 animals); 2.75 g/kg: 3/5; 3.57-5.00 g/kg: 5/5;

Females: 1.30 g/kg: 0/5; 1.82 g/kg: 2/5; 2.55 g/kg: 3/5; 3.57-5.00 g/kg: 5/5.

 

Aluminium potassium fluoride NK FLUX (AT-2-NK):

Males: 3.57 g/kg: 0/5 (0 of 5 animals); 5.00 g/kg: 3/5; 7.00 g/kg: 5/5;

Females: 2.55 g/kg: 0/5; 3.57 g/kg: 0/5; 4.25 g/kg: 3/5; 5.00 g/kg: 5/5.

 

Aluminium potassium fluoride NK FLUX (AT-3-NL):

Males: 3.57 g/kg: 1/5 (1 of 5 animals); 5.00 g/kg: 3/5; 7.00 g/kg: 5/5;

Females: 2.55 g/kg: 0/5; 2.75 g/kg: 3/5; 3.00 g/kg: 5/5; 3.57 g/kg: 5/5; 5.00 g/kg: 5/5.

 

In the animals which died histopathological lesions were observed mainly in the gastro-intestinal tract, primarily in the stomach.

The most critical LD50 values were observed when testing aluminium potassium fluoride 100 FLUX (AT-1-KC): for males the LD50 value was 2.72 (2.52-2.93) g/kg bw and for females the LD50 value was 2.15 (1.61-2.89) g/kg bw.

Inhalation route

Two acute inhalation toxicity studies with rats are available (American Biogenics Corporation, 1985a,b). In the first study, one group of 5 male and 5 female rats was exposed to 4.92 mg/L multiconstituent aluminium potassium fluoride for 1 hour, followed by an observation period of 14 days. 1 male and 3 females died. Thus the LC50 for 1 hour was >4.92 mg/L. Clinical signs that were reported were irregular breathing, poor coat quality, yellow/brown stained fur, lethargy, crusty eye, crusty nose and crusty muzzle. Abnormalities of the stomach (multifocal erosions, diffuse red brown discoloration of glandular mucosa), glandular stomach (mucosa smooth and discolored red brown), heart (diffusely pale, tan discoloration, mottling) and small intestine (dark contents) were observed in 2 males and 3 females.

In the second study, one group of 5 male and 5 female rats was exposed to 3.4 mg/L aluminium potassium fluoride for 1 hour, followed by an observation period of 14 days. One female died. Thus de LC50 for 1 hour was >3.4 mg/L. Clinical signs that were reported were irregular breathing, ataxia, lethargy and crusty nose. No gross abnormalities in the survivors were noted. Abnormalities of the heart and stomach were observed in the female that died during the study.

Using modified Haber's law (Cnx t = constant) and using n=1 as a default value in accordance with Chapter R.7.4.4.1 of REACH Guidance on information requirements and chemical safety assessment for extrapolation from shorter to longer exposure duration, the 4 h LC50 is calculated to be >1.23 mg/L (starting point for this calculation is the highest level of 4.92 mg/L/1h at which 1 male and 3 female rats died). As at the extrapolated 4 h figure, 1.23 mg/L, the mortality number was 4/10 animals and as the classification limits for aerosols/particulates for classification as harmful are: 1 < LC50 ≤ 5 mg/L/4h, it is expected that the LC50 figure of the substance falls within the classification range for harmful.

Supporting data for not classifying the substance in a higher category is the result that no mortality was observed when rats were exposed 6 hours/day, 5 days/week for 28 days up to a concentration of 0.6 mg/L aluminium potassium fluoride (see section on repeated dose toxicity).

Dermal route

Regarding the dermal route, three studies (equivalent or similar to OECD guideline 402) are available (Hazleton Laboratories, 1985d,e,f). Different multiconstituent aluminium potassium fluoride batches were tested: aluminium potassium fluoride 100 FLUX (AT-1 -KC), aluminium potassium fluoride NK FLUX (AT-2 -NK) and aluminium potassium fluoride NK FLUX (AT-3 -NL). In the studies, five male and five female rabbits were administered a single dermal dose of 2.0 g/kg bw and held for an observation period of 14 days. No mortality and no other effects were observed and/or reported. The LD50 value was >2.0 g/kg bw for all three tested batches of aluminium potassium fluoride.

Justification for classification or non-classification

Based on the results of the available acute toxicity studies, no classification is warranted for acute oral and dermal toxicity. Regarding the inhalation route of exposure, in accordance to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance has to be classified as Cat. 4; H332.