Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

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other: GLP compliant, non-guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Sample number: 41105734

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:
not performed
Effect levels
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.

Applicant's summary and conclusion

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.