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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
First exposure to test substance 19 Apr, 1996 to 3 May, 1996.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study with acceptable restrictions. Al3+is the predominant aluminium form at low pH (less than 5.5). As pH increases above 5.5, aluminium-hydroxide complexes formed by hydrolysis become increasingly important and dominate aqueous aluminium speciation . Al3+, depending on the composition of the medium and pH, may form Al(OH)3 or Al2O3 or AlCl or AlNO3 or AlSO4 According to the solubility studies, the major elements found at the maximum solubility are 1054 mg/l Al and 856 mg/l Ca, for 100 g of the tested substance, ie approximatively 1%. A read-across was made with all the aluminium salts and oxides.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
other: EPA 40 CFR 158 Guideline Reference #81-3
Deviations:
yes
Remarks:
: Only one concentration was used; no justification was provided for the choice of concentration used.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: Only one concentration was used; no justification was provided for the choice of concentration used.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: Fumed alumina
Supplier: Cabot Corporation
Purity: Not reported
Batch Number: Lot PP-E-15-5 Bag 183.
Storage: Not reported
Levels of impurities: Not reported
Physical description: white powder.

The sponsor (Cabot Corporation) was responsible for evaluations related to chemical composition, purity, strength, stability and other data required by 21 CFR Part 58.105, 40 CFR Parts 160.105 and 792.105. This information was not provided in the report.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: ca. 8 – 11 weeks (born between 7 Feb and 29 Feb, 1996; received at facility 9 Apr, 1996; start date of experiment 19 Apr, 1996)
- Weight at study initiation: 219-276g for males, 222-273g for females
- Housing: The rats were identified using cage notation and tail marks and housed one animal per cage in suspended cages. Bedding was beneath cages and was changed at least 3x per week.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 day acclimation period.

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: Not relevant.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 57 liter dynamic glass chambers divided into ten non-restraining cubicles with wire screening
- Source and rate of air: The airflow exchanged the chamber volume 10 to 15 times per hour and was also recorded at 30 minute intervals during the exposure period. Chamber air flow was 30 L/min initially and at all times points during exposure except at 100 minutes when a value of 20 L/min is reported in the results.
- System of generating particulates/aerosols: To produce the test concentration, the fumed alumina was fed into a Venturi Dust Generator (Intox). Air flow was adjusted to ensure a uniform concentration of the test compound in the chamber.
- Temperature, humidity, pressure in air chamber: Chamber temperature and humidity were monitored at 30 minutes intervals during the exposure. The temperature ranged from 20.7 to 23.3ºC and the humidity from 60 to 61% during the exposure period.


TEST ATMOSPHERE (if not tabulated)
Details on analytical verification of doses or concentrations:
A nominal concentration was calculated by dividing the amount of test substance dispensed from the dust generator during the 4 hour exposure period by the total volume of air that passed through the chamber. The amount of test material was determined gravimetrically using pre-weighed filters that sampled for 2 minutes at 3 litres per minute air flow.

Particle size MMAD (mass median aerodynamic diameter)/GSD (geometric standard deviation):
The particle size distribution was measured twice during exposure using an 8-stage Andersen cascade impactor. The mass mean aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined graphically using log-probit paper. During a pre-test evaluation, an MMAD of ≤4µm was required to meet the definition of “respirable” sized particles.

During the experiment, the MMAD was 2.31 µm and the GSD 2.97 in the first 30 second sampling period and 2.85 µm and 3.22 in a second sampling period.




Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Single dose: 2.3 mg/L
The average gravimetrically determined concentration of test substance in the chamber air was 2.3 mg/L (sd. 0.041, n=6).
No. of animals per sex per dose:
Ten animals (5 male and 5 female) were treated.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed for signs of toxicity at approximately one hour intervals during exposure, one hour post exposure and daily during the 14 day post-exposure observation period. Observations were twice daily for mortality. Body weights were recorded pre-test, weekly and at termination
- Other examinations performed:
Animals were observed for signs of toxicity, mortality and pharmacological effects.
Body weights were also recorded. Gross pathology was examined post-mortem.

Sacrifice and Pathology (methods):
BeuthanasiaR was used to sacrifice the animals.
Statistics:
No methods were used.

Results and discussion

Preliminary study:
Not relevant.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.3 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Slope: could not be calculated.
Mortality:
There were no deaths during the exposure or 14 day post-exposure observation period.
Clinical signs:
other: All animals had closed eyes, a wet nose/mouth area and fur coated with the test material at 45 minutes, 93 minutes, 155 minutes and 215 minutes during the exposure period. At 1 hour post-exposure, only coated fur was noted, again for all animals. All an
Body weight:
The authors report normal weight gain in all males but in only 1 of the 5 females. Weight loss was observed in two females on day 7 of the post-exposure period and in another two females on day 14.
Gross pathology:
Lungs were darker than normal (score of 2) with slight or scattered red areas in one female. No other abnormalities were observed.

Any other information on results incl. tables

Body Weight (g)

Animal

Pre-test

Day 7

Day 14

1-M

265

321

349

2-M

276

319

349

3-M

266

313

342

4-M

219

271

296

5-M

274

339

387

Mean

260

313

345

sd

23.4

25.2

32.4

6-F

264

254

277

7-F

226

238

241

8-F

273

250

269

9-F

230

246

238

10-F

222

252

236

Mean

243

248

252

sd

23.7

6.3

19.3

 

The authors report normal weight gain in all males but in only 1 of the 5 females. Weight loss was observed in two females on day 7 of the post-exposure period and in another two females on day 14.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No mortality was observed during this study, clinical signs were minor and only one animal showed lung abnormalities on necropsy. A detrimental effect on weight gain was observed in females only. The LC50 for fumed alumina is greater than 2.3 mg/L.
Executive summary:

The study by Cabot (1996) was conducted according to EPA Guidelines for Test Procedures Subdivision F, Series 81-3 and TSCA 40 CFR 798.1150. Five healthy male and five healthy female Wistar Albino rats were exposed to fumed alumina in an inhalation chamber for 4 hours. The number of animals used and the exposure duration were adequate according to the guidelines. The air concentration in the chamber, determined gravimetrically, was 2.3 mg/L.  Only one concentration was tested. The average mass median diameter was 2.58µm with a geometric standard deviation of 3.10 µm (2.31 µm, GSD 2.97 in the first 30 second sampling period and 2.85 µm, GSD 3.22 in a second sampling period). Chamber airflow, temperature (20.7 – 23.3ºC) and humidity (60 to 61%) were monitored throughout the exposure period. Animals were observed for signs of toxicity at approximately one hour intervals during exposure, at one hour post exposure and then daily during a 14 day exposure period. Body weights were recorded pre-test, weekly and at termination.  No deaths were observed during exposure or during the 14 day post-exposure period. All animals had closed eyes, wet nose/mouth areas and fur coated with the test materials during the exposure. Observations were normal during the 14-day post-exposure period. Weight gain was normal in all the male animals. Weight loss was observed in two females on day 7 of the post-exposure period and in another two females on day 14. Lungs that were darker than normal with red areas were observed in only one female on necropsy. Based on the results of this study, the LC50is greater than 2.3 mg/L. The main limitations of this study were the lack of description of the test materials and the use of only one concentration with no rationale provided for the level chosen. A Klimisch Score of 2 (reliable with restrictions) is considered appropriate.