Aluminum sodium oxide

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:

supporting study

Study period:

1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. GLP-compliant. Short period of post-exposure observations.

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

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

short period of post-exposure observations

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Catapal Alumina (75 % aluminium oxide, 25% aluminium hydroxide)

IUPAC Name:

Catapal Alumina (75 % aluminium oxide, 25% aluminium hydroxide)

Details on test material:

- Name of test material (as cited in study report): Catapal Alumina Fines
- Supplier: Vista Chemical Company , Houston, Texas, 77224
- Physical state: white powder
- Analytical purity: no data
- Composition of test material, percentage of components: 75% aluminium oxide, 25% aluminium hydroxide
- Lot/batch No.: LOT 2169 V3612B
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

other: HSD (SD) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Houston, Texas
- Age at study initiation: adults
- Weight at study initiation: males (272-337 g), females (204-264 g)
- Housing: 1-3 per cage (males separated from females); 1 per cage during exposure period
- Diet (e.g. ad libitum): : Purina Formulab Chow #5008 (ad libitum), except during the exposure period
- Water (e.g. ad libitum): tap water (ad libitum) from automatic water system, except during the exposure period
- Acclimation period: at least 1 week

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: During the exposure period, Al-treated and control groups were placed in individual, stainless steel cages with a 500 L stainless steel, New York University design, dynamic flow inhalation chamber.
- Exposure chamber volume: 500 L
- System of generating particulates/aerosols: The aerosol was generated by 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 into the chamber was maintained through the use of a calibrated critical orifice. Air flow was monitored at 30 minute intervals during the exposure period and was sufficient to keep adequate oxygen content of the exposure atmosphere. Temperature and humidity were monitored at 30 minute intervals during the exposure period from a Taylor wet bulb/dry bulb hydrometer located in the exposure chamber.
- Method of particle size determination: The particle size was measured using an Andersen cascade impactor.
- Chamber operating parameters:
Relative humidity (%)
Control group:
Relative humidity mean: 80%
Relative humidity range: 77-86%
5.09 mg/L group:
Relative humidity mean: 71%
Relative humidity range: 67-76%

Temperature (°C):
Control group:
Temperature mean: 71 °F/ 22 °C
Temperature range: 70-720 °F
5.09 mg/L group:
Temperature mean: 68 °F / 20 °C
Temperature range: 67-69 °F

Chamber flow rate (Lpm):
Control group: 82.0
5.09 mg/L group: 91.7

TEST ATMOSPHERE
- Brief description of analytical method used: The actual exposure concentration of test material at the breathing zone of the animals was determined gravimetrically 2 times per hour. The gravimetric concentration was determined by dividing the total mass of test material obtained by filter analysis by a known volume of air which passed through the filter. The nominal concentration was determined by dividing the loss in weight of the test material after the exposure by the total volume of air passed through the chamber.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: see “Any other information on materials and methods incl. tables”
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
2.75 h distribution: 5.423 / 3.038 µm
4 h distribution: 4.645 / 3.162 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The actual exposure concentration of test material at the breathing zone of the animals was determined gravimetrically 2 times per hour.

Duration of exposure:

4 h

Concentrations:

Mean exposure concentration (0-4 h): 5.09 mg/L (range: 4.28-5.88 mg/L)

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 72 h
- Frequency of observations and weighing: Daily, before and after exposure, all animals were examined for toxic signs. The animals were weighed before and during the post-exposure period. General appearance of treated and control animals, toxic signs and time of death (if occurred) 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 h, 2 and 3 days of post-exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: The gross necropsy examination was conducted on each of the control and Al treated animals at scheduled sacrifice at termination of the study. 5/5 males and 5/5 females were randomly selected from Al treated and control groups for sacrifice and gross necropsy examination at 24 and 72 hours after exposure, respectively.
Nasal turbinate, lungs and trachea from were removed, fixed in 10% neutral buffered formalin for gross and microscopic histopathology examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.09 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: post-exposure observation perriod: 72 h

Mortality:

No deaths were observed in Al-exposed male and female rats at any observation terms.

Clinical signs:

other: Healthy animals were used in this study. All control male and female rats appeared normal for the duration of the acute inhalation study and the post-exposure period of observation. Clinical sings observed in Catapal Alumina - exposed male and female ra

Body weight:

No changes in body weight were observed following inhalation exposure for 4 h to a high concentration of Catapal Alumina Fines at 24 and 72 h of post-exposure.

Gross pathology:

No observable abnormalities were recorded during gross necropsy examination after 24 and 72 h of post exposure in both male and female rats from Al-treated and control groups.

Other findings:

- Histopathology: The authors reported (qualitatively) that no histopathological abnormalities were observed in nasal turbinate, lungs and trachea during microscopic histological examination in any of the treated or untreated animals.

Any other information on results incl. tables

Table 1. Clinical sings observed in Catapal Alumina Fines - exposed male and female rats at different time points after exposure started

 

Reaction and 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
Activity 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
Note: Severity signs: v-very slight, s-slight; m-moderate, e-extreme ( no details were provided regarding severity ranking in the exposed animals) ; *- “ Due to chamber design, only ten animals (five males and five females) could be observed during the exposure period”; **- “Unable to observe animals at this time period due to excessive collection of test material of the chamber window”.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, no irritation/ pulmonary effects and no mortality were observed in both male and female rats following the acute inhalation exposure to 5.09 mg/L of Catapal Alumina Fines when administered undiluted as an aerosol for 4 h. It should be noted that this high concentration greatly exceeds workers exposure.

Executive summary:

In summary, no irritation effects were observed in male and female rats following an acute inhalation exposure to Catapal Alumina Fines at exposure concentration of 5.09 mg/L (5,090 mg/m3) under conducted experimental conditions.

This study was conducted for Vista Chemical Company, using Vista Catapal Alumina. Stillmeadow, Inc. (1990) investigated the acute inhalation irritation properties of Catapal Alumina Fines (fine powder) (LOT 2169 V3612B) in rats in the GLP-compliant study. The main aim of this study was to “determine the acute inhalation irritation potential of the Catapal Alumina Fines”.

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. During the exposure period, Al- treated and control groups were placed in individual, stainless steel cages with a 500 L stainless steel, New York University design, dynamic flow inhalation chamber. 20 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 aerosol was generated by 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 into the chamber was maintained through the use of a calibrated critical orifice. Air flow was monitored at 30 minute intervals during the exposure period and was sufficient to keep adequate oxygen content of the exposure atmosphere. Temperature and humidity were monitored at 30 minute intervals during the exposure period from a Taylor wet bulb/dry bulb hydrometer located in the exposure chamber.

The actual exposure concentration of test material at the breathing zone of the animals was determined gravimetrically 2 times per hour. The nominal concentration was determined by dividing the loss in weight of the test material after the exposure by the total volume of air passed through the chamber. Particle size determinations were performed by using an Andersen cascade impactor. The exposure concentration determined gravimetrically was 5.09 mg/L or 5,090 mg/m3. 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 - 3.16microns) (4 hours distribution data).

Clinical observations were performed on all animals daily, before and after exposure. The animals were weighed before study and during the 24, 48 and 72 hours of the post-exposure period. The body weight of all animals was recorded before exposure and at 1 and 3 days after the termination of exposure. General appearance of Al treated and control animals, toxic signs and time of death (if occurred) 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, 2 and 3 days of post-exposure. Animals were sacrificed at one and 3 days after the termination of exposure. The gross necropsy examination was conducted on each of the Al treated and control animals (5/5 males and 5/5 females were randomly selected from Al treated and control groups) at 24 and 72 hours after exposure, respectively. 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 in male or female rats following acute inhalation exposure to undiluted test material as an aerosol at a level of 5.09 mg/L for 4 hours during 3 days of the post-exposure observation period. 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. The use of both sexes of animals revealed no significant differences in the sex sensitivity to test material. Because no mortality cases were observed in Al treated male and female rats, the results do not allow estimating the LC50. The authors suggested that the acute inhalation LC50 for Catapal Alumina Fines is greater than 5.09 mg/L (5,090 mg/m3).

Overall, this GLP compliant study was well-reported and has been well-conducted. The main goal of the study was to determine the acute inhalation irritation potential of the Catapal Alumina Fines. Although no guideline was mentioned explicitly, the study appears to have been conducted to conform generally to guidance criteria on acute inhalation toxicity testing (OECD TG 39, OECD TG 436 and OECD TG 403). The 4 hour exposure period conforms to acute inhalation toxicity guidelines and sufficient numbers of animals of both sexes were used. Chamber atmosphere samples were taken from the vicinity of the animals’ breathing zone. The airflow was monitored at regular intervals to detect possible changes in the exposure concentrations. Deviation of the individual chamber concentration samples from the mean chamber concentration did not exceed 20%. In addition, the mass concentration obtained by particle size analysis is within reasonable limit of the mass concentration obtained by filter analyses which suggests that were no considerable sampling errors. Concentrations were gravimetrically verified. Clinical signs observed in all male and female rats during exposure period were short-term and reversible and included decreased activity, piloerection and ptosis. These clinical signs were not observed in Al exposed male and female rats at 24, 48 and 72 hours after the termination of the exposure. The authors suggested that the acute inhalation LC50 for Catapal Alumina Fines is greater than 5.09 mg/L when administered undiluted as aerosol to albino rats. However, some caution is required in interpreting results and a conclusion due to a short period of post exposure observation (3 days instead of 14 days).The main limitations of this study include and a short period of post exposure observations. Based on the overall study design and available limitations, a Klimisch score of 2 (reliable with restrictions) is appropriate for this study.