Ceramic materials and wares, chemicals

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

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: Comparable to guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

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.

Test guideline 2

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

Test material information

Constituent 1

Reference substance name:

Fumed alumina

IUPAC Name:

Fumed alumina

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: 219-276 g for males, 222-273 g 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 23.3 ºC 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 – 23.3 ºC) 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.