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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
26. Feb. 1990 - 29. Feb. 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No justification given for concentration tested, study was terminated shortly after exposure (3 days), observation period should have lasted for 14 days.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
short period of post exposure observations and no justification for test concentration given
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Catapal Alumina Fines
- Physical state: white powder
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
naive albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Houston, Texas
- Age at study initiation: young adult
- Weight at study initiation: males (272 - 337 g), females (204 - 264 g)
- Fasting period before study:
- Housing: 1 - 3 per cage (males separated from females) in suspended, wire bottom, stainless steel cages, during exposure animals were kept one per cage
- Diet: Purina Formulab Chow #5008, ad libitum except during exposure period
- Water: tap water, ad libitum from automatic water system, except during exposure period
- Acclimation period: at least one week

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel dynamic flow inhalation chamber
- Exposure chamber volume: 500 L
- Method of holding animals in test chamber: in cages, with one animal per cage
- Source and rate of air: filtered air
- Method of conditioning air: concentrated aerosol was diluted with filtered air and drawn into exposure chamber
- System of generating particulates/aerosols: The aerosol was generated using a Gem T Trost Air Mill coupled with a motor driven revolving disc delivery system and then combined with filtered air and drawn into the exposure chamber. Air flow in the chamber was maintained through the use of a calibrated critical orifice.
- Method of particle size determination: was done using an Andersen cascade impactor
- Temperature, humidity in air chamber: control group - temp.: 21 - 22°C; humidity: 77 - 86 %, treatment group - temp.: 19.5 - 20.5°C; humidity: 67-76 %

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of test material in the exposure atmosphere was determined gravimetrically twice per hour and nominally at the end of the exposure period. The gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and the dividing the amount of test material deposited on the filter by the volume of air which passed through the filter. The nominal concentration was determined by dividing the loss in the weight of the test material after the exposure by the total volume of air which passed through the chamber.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see table1 under any other informations on materials and methods including tables
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): at 2,75 hours - 5.423 µm/3.038 µm; at 4 hours - 4.645 µm/3.162 µm

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: not given
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetricalls
Duration of exposure:
4 h
Concentrations:
5.09 mg/L
No. of animals per sex per dose:
10 males and 10 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 72 hours post exposure
- Frequency of observations and weighing: weighing - before and during the post-exposure period, general observations, toxic signs and mortality were recorded at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 24 hours and 2 and 3 days post exposure
- Necropsy of survivors performed: yes (at 24 and 72 hours after exposure)
- Other examinations performed: clinical signs, body weight, histopathology of nasal turbinates, lung and trachea
Statistics:
Particle size distribution was calculated by using Probit analysis, Finney, D.J.: Probit analysis, 3rd Edition, Chapter 3 and 4, 1971, Cambridge University Press; Statistical analysis were conducted using 48 K APPLE II PLUS computers

Results and discussion

Preliminary study:
Not available
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.09 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths were observed in Al-exposed male and female rats at any observation time.
Clinical signs:
other: Control animals did not show any clinical signs during the study. Treated animals showed piloerection, decreased activity and ptosis (see summary table3). Piloerection and decreased activity were slightly more prominent in females than in males. All signs
Body weight:
No changes in body weight were observed following inhalation exposure for 4 hours to high concentration of Catapal Alumina Fines at 24 and 72 hours post exposure.
Gross pathology:
No observable abnormalities were recorded during gross necropsy examination after 24 and 72 hours of post exposure in both males and females.
Other findings:
- Organ weights: not reported
- Histopathology: No histopathological abnormalities were observed in nasal turbinate, lungs and trachea during microscopic histological examination in any of the treated animals.

Any other information on results incl. tables

Table7.2.2/3: Clinical signs observed

Reactionand severity  Time after exposure period started
Hours*
 0.5  1.0  1.5  2.0  2.5  3.0  3.5  4.0  4.5  5.0  5.5  6.0  24  48  72

Males

Piloerection (s-e)  5  5  5  5  5  5  **  **  10  10  10  0  0  0  0
Acitivty decreased (s)  0  5  5  5  5  5  **  **  10  10  0  0  0  0  0
Ptosis (s)  0  5  5  5  5  5  **  **  0  0  0  0  0  0  0

Females

Piloerection (s-e)   5  5  5  5  5  5  **  **  10  10  10  10  0  0  0
Activity decreased (s)   0  5  5  5  5  5  **  **  10  10  10  0  0  0  0
Ptosis (s)   0  5  5  5  5  5  **  **  0  0  0  0  0  0  0

Severity signs: v-very slight, s-slight, m-moderate, e-extreme (no details provided regarding severity ranking in the exposed animals)

*- Due to chamber design only ten animals (5 males, 5 females) could be observed during exposure period.

**- Unable to observe animals at this point due to excessive collection of test material of the chamber window.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions of this study, the inhalatory LC50 value of Catapal Alumina Fines when administered undiluted as an aerosol for 4 hours in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, ten male and ten female rats were exposed for four hours to an aerosol generated from the undiluted test material (fine powder) at an exposure concentration of 5.09 mg/L or 5,090 mg/m3. Twenty animals (negative control group) were housed in the same manner in an identical inhalation chamber for 4 hours without exposure to the test material. All animal were returned to their laboratory cages within 24 hours after termination of exposure. The actual exposure concentration of test material at the breathing zone of the animals was determined gravimetrically 2 times per hour. The mass median aerodynamic diameter (MMAD) for the Catapal Alumina fine powder particles (fine powder administered undiluted as an aerosol) was 4.64 microns (geometric standard deviation - 3.16 microns) (4 hours distribution data). Animals were then observed for mortality, clinical signs and body weights and were all sacrificed for macroscopic examination (Day 3). Nasal turbinate, lungs and trachea from all Al exposed and control group animals were removed, fixed in 10% neutral buffered formalin for microscopic histopathology examination.

 

No mortality was observed. Clinical signs of piloerection were noted in male and female rats during exposure period and in all males and females during 1.5 hours and 2.0 hours post administration, respectively. Decreased activity was observed in the treated male and female rats during exposure period and 1.0 hour and 1.5 hours post administration, respectively. Ptosis was observed in the treated male and female rats during exposure period only. All animals appeared to be normal and no toxic signs were observed at 24, 48 and 72 hours post administration. No body weight changes were noted during the post-exposure observation period. Macroscopic examination at the end of the 24 and 72 observation periods did not reveal any aluminium-related changes of the internal organs of the treated animals compared to the control group. The results showed no histopathological changes in the nasal turbinate, trachea and lungs of the Catapal Alumina exposed animals.

Under the test conditions of this study, the inhalatory LC50, 4h value of (aerosol) in rats was considered to exceed 5 mg/L. Based on these results, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.