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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Adequacy of study:
other information
Study period:
1986
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study was not conducted according to guidelines.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986
Report Date:
1985

Materials and methods

Principles of method if other than guideline:
Alluminum ammonium sulfate was administered to CD1 male and female mice at dose level of 1.47-3.81 mg/m3 SO4 and then respiratory infected with Streptococcus Zooepidemicus.

Mortality, pulmonary bactericidal activity, pulmonary cell number, type, viability, ATP content and pulmonary morphology were studied. Tracheal ciliary beating frequency and morphology were also studied in CD1 mice and Syrian golden hamsters.
GLP compliance:
not specified
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): aluminum ammonium sulfate
- Molecular formula (if other than submission substance): Al2(SO4)3(NH4)2 SO4-24H2O
- Substance type: no data
- Physical state: no data
- Analytical purity: 99.9%
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI
- Age at study initiation: 3-4 week old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: plastic shoe box cages before exposure, in special stainless steel wire-mesh cages during exposure, which held up to 24 animals in
individual compartments
- Diet (e.g. ad libitum): freely avalaible, except during exposure periods.
- Water (e.g. ad libitum): freely avalaible, except during exposure periods.
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): during the exposure, the temperature ranged from 23 to 30°C
- Humidity (%): during the exposure, the humidity ranged from 30 to 50% RH
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a nebulizer (Model 40, DeVilbiss Co., Somerset, PA)
- Exposure chamber volume: 432 liter (120 x 60 x 60 cm)
- Method of holding animals in test chamber: in special stainless steel wire-mesh cages during exposure, which held up to 24 animals in individual
compartments
- Source and rate of air: no data
- Method of conditioning air: no data
- System of generating particulates/aerosols: aerosol was generated by means of a nebulizer (Model 40, DeVilbiss Co., Somerset, PA) containing a 1% (w/v) aqueous solutions of aluminum ammonium sulfate
- Method of particle size determination: determined with an eight-stage cascade impactor (Inhalation Toxicology Research Institute, Albuquerque, N.M.)
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: the temperature ranged from 23 to 30°C and the humidity ranged from 30 to 50% RH

TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: the aerosol mass concentration in the chamber was determined from two replicate samples collected over the 3-hr exposure period on 47mm diameter 0.2 µm Millipore filters.

VEHICLE
- Composition of vehicle (if applicable): no data
- Concentration of test material in vehicle (if applicable): no data
- Justification of choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: no data
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = 0.75µm with a g of 2.00

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: no data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
3 h
Concentrations:
1.47-3.81 mg/m3 SO4
No. of animals per sex per dose:
See table 7.2.2/1
Control animals:
yes
Details on study design:
No additional data

Results and discussion

Preliminary study:
No data
Mortality:
The mortality rate was increased and MST was decreased in all groups of mice exposed to alluminum ammonium sulfate and then challenged with the infection aerosol.
However, the difference between treatment groups were, in general, not significant. When the data were subjected to a log-linear analysis, the only significant effect on mortality was a main effect of experimental group; i. e. the aerosol-exposed mice had a higher mortality rate (P<0.05) when averaged over both sexes and the three concentrations. The concentration-response was not linear and there were no between-sex differences.
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
Pulmonary free cells: No significant changes in total cell counts were detected in mice exposed to Alluminum ammonium sulfate. However, both male and female mice did show significantly increased pulmonary cellular ATP levels immediatly after exposure to the high concentration of Alluminum ammonium sulfate.
Pulmonary bactericidal activity: significantly increased in male mice exposed to the intermediate level of Alluminum ammonium sulfate. The effects of the high concentration were not determined.
Tracheal epithelium: Significantly decreased cilia beating frequency was seen only in hamsters exposed to the high concentration of Allumnum ammonium sulfate. Cytologic alterations were observed in the tracheal epithelium of sulfate-exposed hamsters. Significant decreases in percentage normal epithelium were seen in hamsters after exposure to Alluminum ammonium sulfate. No exposure-related changes in percentage normal epithelium were observed in mice.
SEM examination of the respiratory tract: No cellular damage was observed in the respitory tracts of mice exposed to Alluminum ammonium sulfate.

Any other information on results incl. tables

Table 7.2.2 /2: Changes in mortality and mean survival time of mice after a single 3 -hr exposure to aluminum ammonium sulfate and challenge with aerosols of streptococcus

 

Mg SO4/m3(calculated mg metal/m3)

Sex

Number of mice

Change in mortalitya(%)

Change in mean survival timea(day)

Control

SO4

Aluminum ammonium sulfate

3.79

M

24

24

+ 16.7

- 1.3

0.53

F

23

+ 13.2

- 1.2

2.10

M

48

49

+ 5.2

- 0.8

0.30

F

50

+ 27.0*

- 2.3**

1.47

M

24

24

+ 16.7

- 1.5

0.21

F

24

+ 8.3

- 1.0

aSulfate-exposed minus control animals. Significant difference between sulfate-exposed and corresponding infected control groups. (Bonferoni adjusted probability values, *P<0.05, **P<0.01).

Table 7.2.2/3: Effects of single 3-hr exposure to aerosol of aluminum ammonium sulfate on pulmonary bacterial activity

 

 

Mg SO4/m3(mg metal/m3)

Interval between exposure and assay (hr)

Sex

Pulmonary free cells

Bactericidal activity: K. pneumoniae killed

Total cells (count x 105)

Cellular ATP (108fg/105cells)

na

%b

na

%b

na

%b

Aluminum ammonium sulfate

3.79

0.53

 

2.10

0.30

 

 

 

<1

 

 

<1

 

 

24

 

M

F

 

M

F

 

M

F

16

16

 

16

16

 

32

32

79.3

122.6

 

200.9

111.7

 

84.3

126.8

15

16

 

16

16

 

31

32

170.1**

213.6**

 

89.3

121.6

 

79.8

92.0

 

 

 

20

18

 

 

 

N.D.

N.D.

 

127.7**

113.1

 

N.D.

N.D.

aNumber of mice

bPercentage of control value. Significantly different than corresponding control mice exposed to filtered air (Bonferoni adjusted probability values, *P<0.05, **P<0.01).

cN.D., not done

Table 7.2.2/4: Cilia beating frequency and percentage normal epithelium in hamster and mouse trachea immediatly after a single 3 -hr exposure to aluminum ammonium sulfate

 

SO4Conc. (mg/m3)

Mean ciliaa(beats/min)

Normal epitheliumb (%)

Mouse

Hamster

Mouse

Hamster

Air

SO4

Air

SO4

Air

SO4

Air

SO4

Aluminum

ammonium sulfate

3.79

2.10

N.D.

1322

N.D.

1320

1216

1261

1143*

1231

N.D.

77

N.D.

65

93

93

59*

86

aMean of 48 observations of 12 tracheal rings from four animals.

bMean of 12 tracheal rings from four animals. Normal tracheal epithelium is defined as a smooth surface with beating cilia.

cBubbling of epithelium with debris present: cilia movement was visible and appeared normal, but quantitative evaluation could not be made

dN.D., not done

* Significant difference from control animals exposed to filtered air (P<0.05).

Applicant's summary and conclusion

Interpretation of results:
other: not useful to conclude on classification
Remarks:
Criteria used for interpretation of results: EU
Executive summary:

In an in vivo inhalation study, Aluminum ammonium sulfate was administered to CD1 male and female mice at dose level of 1.47-3.81 mg/m3 SO4 and then respiratory infected with Streptococcus Zooepidemicus.

Mortality, pulmonary bactericidal activity, pulmonary cell number, type, viability, ATP content and pulmonary morphology were studied. Tracheal ciliary beating frequency and morphology were also studied in CD1 mice and syrian golden hamsters.

After exposure to the highest concentration of Aluminum ammonium sulfate, significant changes were observed in cellular ATP levels in mice, in tracheal cilia beating frequency and in normal epithelial in hamsters.

There was no significant increase of mortality in mice at the high concentration, and no apparent concentration relashionship or between-sex difference.

With the intermediate concentration of Aluminum ammonium sulfate, effects were seen in mortality rate and MST (females only), and pulmonary bactericidal activity (males only).

Aluminum ammonium sulfate was less toxic than Cupric sulfate and Aluminum sulfate by inhalation way.