Registration Dossier
Registration Dossier
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EC number: 215-691-6 | CAS number: 1344-28-1
Endpoint summary
Administrative data
Description of key information
Skin irritation (similar OECD 404, rabbit): not irritating
Eye irritation (similar FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) and OECD 405, rabbit): not irritating
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- : longer duration of exposure (24 versus 4 hours); limited details on test material and test conditions
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: intact or abraded skin
- Vehicle:
- not specified
- Controls:
- no
- Amount / concentration applied:
- 0.5 g of the solid test substance was brought into contact with the intact or abraded skin under a surgical patch measuring 1 inch Χ 1 inch.
- Duration of treatment / exposure:
- 24 hours
- Observation period:
- 24 hours and 72 hours after the substance application
- Number of animals:
- 6 rabbits were treated on intact skin and 6 on abraded skin.
- Details on study design:
- TEST SITE
- Area of exposure: the hair was removed from the backs of the animals with an electric clipper avoiding abrasions. The test material was placed under a surgical patch 1 inch Χ 1 inch (2.5 cm Χ 2.5 cm) on intact or abraded skin.
- Type of wrap if used: surgical patch. The patches were fixed to the application site with adhesive tape. The entire trunk of the animals was wrapped with an impervious material to keep the patches in place.
SCORING SYSTEM: Draize scoring system
The abrasions were “minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.”
The patches were fixed to the application site with adhesive tape. The entire trunk of the animals was wrapped with an impervious material to keep the patches in place
After exposure for 24 hours, the patches and the test material were removed (no information was provided on washing of the skin after patch removal.)
Skin lesions were evaluated at the time of patch and material removal and 48 hours later (24 and 72 hours after the application)
Scoring systems applied:
-24 hours after application -method of Draize (J. Pharmocol. 82 (1944) 377-390).
-72 hours after application – CIVO grading system (because the Draize scoring system does not describe scaliness and necrosis)
Evaluation of skin reactions (Draize, 1944) Value
A. Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
B. Edema formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond the area of exposure) 4
Evaluation of skin reactions (CIVO) Value
No reaction at all 0
Very slight scaliness 1
Distinct scaliness or very slight incrustation 2
Distinct incrustation 3
Severe incrustation 4 - Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- of 6 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 72 h
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritant / corrosive response data:
- Overall, the test material caused slight erythema in 2 of the 12 rabbits (one - 24 hours after application, and the other - 72 hours after application).
- Other effects:
- Clinical signs of toxicity were not reported
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The observed slight erythema effects do not lead to a classification for the test item. Therefore AK 43/79 is not considered to be a primary skin irritant.
- Executive summary:
This study conducted for Degussa corporation investigated dermal irritation effects of aluminium oxide in New Zealand White albino rabbits. 0.5 g of the test substance was placed on the intact or abraded skin of the rabbits under a surgical patch measuring 2.5 Χ 2.5 cm. Six rabbits had intact skin and six rabbits abraded skin. The exposure continued for 24 hours (a 4 hour exposure is recommended by OECD 404), and skin lesions were scored immediately after patch removal and 48 hours later (24 and 72 hours after the application of the test material). Two sets of scoring criteria were used: Draize (1944) - 24 hours after the material application and CIVO - 72 hours after the application.
Insufficient information was provided on the test material and in what form it was applied to the skin. No information was provided on animal husbandry. Slight erythema was observed on the intact skin of 2 animals (one 24 hours after the substance application and the other 72 hours after application). No signs of skin irritation were observed on the abraded skin at any time. The overall primary irritation score from the study (0.2) would not lead to classification.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- : longer duration of exposure (24 versus 4 hours); limited details on test material and test conditions
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Environmental/Housing conditions: No information
Acclimation: No information.
Feeding conditions: No information. - Type of coverage:
- semiocclusive
- Preparation of test site:
- other: intact or abraded skin
- Vehicle:
- not specified
- Controls:
- no
- Amount / concentration applied:
- 0.5 g of the solid test substance was brought into contact with the intact or abraded skin under a surgical patch measuring 1 inch Χ 1 inch.
- Duration of treatment / exposure:
- 24 hours
- Observation period:
- 24 hours and 72 hours after the substance application
- Number of animals:
- 6 rabbits were treated on intact skin and 6 on abraded skin.
- Details on study design:
- TEST SITE
- Area of exposure: the hair was removed from the backs of the animals with an electric clipper avoiding abrasions. The test material was placed under a surgical patch 1 inch Χ 1 inch (2.5 cm Χ 2.5 cm) on the intact or abraded skin.
- Type of wrap if used: surgical patch.The patches were fixed to the application site with adhesive tape. The entire trunk of the animals was wrapped with an impervious material to keep the patches in place.
SCORING SYSTEM: Draize scoring system
The abrasions were “minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.”
The patches were fixed to the application site with adhesive tape. The entire trunk of the animals was wrapped with an impervious material to keep the patches in place and “to retard evaporation of volatile substances.”
After exposure for 24 hours, the patches and the test material were removed (no information on the mode of removal)
Skin lesions were evaluated at the time of patch and material removal and 48 hours later (24 and 72 hours after the application)
Scoring systems applied:
- 24 hours after application -method of Draize (J. Pharmocol. 82 (1944) 377-390).
- 72 hours after application – CIVO grading system (because the Draize scoring system does not describe scaliness and necrosis)
Evaluation of skin reactions (Draize, 1944) Value
A. Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
B. Edema formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond the area of exposure) 4
Evaluation of skin reactions (CIVO) Value
No reaction at all 0
Very slight scaliness 1
Distinct scaliness or very slight incrustation 2
Distinct incrustation 3
Severe incrustation 4 - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- erythema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- 6/6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks:
- No 48 h data are available for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)
- Other effects:
- Clinical signs of toxicity were not reported
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The test item, AK 44/79 caused slight erythema in 2/12 rabbits. The observed effects do not lead to a classification. AK 44/79 is, therefore, not considered to be a primary skin irritant.”
- Executive summary:
This study conducted for Degussa corporation investigated dermal irritation effects of aluminium oxide inNew ZealandWhite albino rabbits.0.5 g of the test substance was placed on the intact or abraded skin of the rabbits under a surgical patch measuring 2.5 Χ 2.5 cm. Six rabbits had intact skin and six rabbits had abraded skin. The exposure continued for 24 hours (4 hour exposure is recommended by OECD 404), and skin lesions were scored immediately after patch removal and 48 later (24 and 72 hours after the application of the test material). Two sets of scoring criteria were used: Draize (1944) - 24 hours after the material application and CIVO - 72 hours after the application.
Insufficient information wss provided on the test material and application of the test material. No information was provided on animal husbandry. Slight erythema was observed on theintactskin of 2 animals 24 hours after the substance application. No signs of skin irritation were seen at 72 hours. No signs of skin irritation were observed on theabradedskin at any time. The overall primary irritation score from the study (0.3 at 24 hours) would not lead to classification.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- : Longer duration of exposure (24 versus 4 hours); no detail on pH of test substance; limited detail on characteristics of the test substance.
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Age: not reported
Sex: not reported
Weight: not reported
Environmental/Housing conditions:
No information provided.
Acclimation: No information was provided.
Feeding conditions:
This information was not provided. - Type of coverage:
- other: wrapped with binders of rubber dam
- Preparation of test site:
- other: intact and abraded skin
- Vehicle:
- water
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
-Concentrations: 0.5g in 1.0mL = 500g/L (50%)
-Volume: 1.0 mL
-Area: the substance was under a 1 inch square patch. - Duration of treatment / exposure:
- A single, 24 hour dermal application was made.
- Observation period:
- Observations were made at 24 and 72 hours.
- Number of animals:
- Three animals with intact skin and three animals with abraded skin
- Details on study design:
- One-inch square gauze patches were applied to pre-moistened, clipped intact or abraded skin on the back of the animals, wrapped with binders of rubber dam and immobilised for the exposure period.
The scoring system used was that of Draize (1959) and was provided in the report:
Evaluation of Skin reactions
Erythema and eschar formation:
No erythema, Score = 0
Very slight erythema (barely perceptible), Score =1
Well-defined erythema, Score=2
Moderate to severe erythema, Score=3
Severe erythema (beet redness) to slight eschar formation (injuries in depth), Score =4
Edema formation:
No edema, Score=0
Very slight edema (barely perceptible), Score=1
Slight edema (edges of area will defined by definite raising), Score=2
Moderate edema (raised approximately 1.0mm)
Severe edema (raised more than 1.0mm extending beyond the area of exposure), Score=4
-“Values for erythema and eschar formation at 24 hours and 72 hours for intact skin animals will be added to the values on abraded skin animals at 24 and 72 hours. Similarly, the values for edema formation at 24 hours and at 72 hours for the intact and abraded skin animals will be added. The primary irritant score is the total of the eight values divided by four. A primary irritant is one which results in a score of five or more as tested by this method.”
The pH of the test substance was not measured. - Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Other effects:
- Clinical signs of toxicity were not reported.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The results from the study are negative and would not lead to classification.
- Executive summary:
A study conducted at Hazleton Laboratories Inc. for the Cabot Corporation investigated dermal irritation effects of ALON, a fumed alumina produced by the chemical hydrolysis of aluminium chloride, in New Zealand White rabbits. 0.5g of the substance in 1.0mL of distilled water was applied to pre-moistened skin on the backs of 6 rabbits under gauze patches. Three of the rabbits had abraded skin and three intact skin. The patches remained place for 24 hours. Lesions were scored at 24 hours and at 72 hours using the scoring criteria of Draize (1959). The report lacks detail on animal husbandry and signs of toxicity. Further details of the test substance characteristics were obtained from the study sponsor. The results showed slight erythema in all three rabbits with abraded skin at 24 hours. The erythema had resolved by 72 hours. No erythema was observed in the animals with intact skin. No animal exhibited edema. The overall primary irritation score from the study (0.25) would not lead to classification.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Summary of available data used for the endpoint assessment of the target substance
- Adequacy of study:
- supporting study
- Justification for type of information:
- Refer to analogue justification provided in IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibilty: not applicable
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The source substances (CAS 21645-51-2) are not considered as irritating to the skin. Applying the read-across approach, the target substance (CAS 1334-28-1) is expected to have a similar skin irritation/ corrosion potential.
Referenceopen allclose all
Individual and average skin reaction scores
1) Intact skin
--------------------------------------------------------------------------------------------
Rabbit number 24 hour 72 hour
A-B A-B
---------------------------------------------------------------------------------------------
8416 0-0 0-0
8417 0-0 0-0
8418 0-0 1-0
8419 0-0 0-0
8420 1-0 0-0
8421 0-0 0-0
--------------------------------------------------------------------------------------------
Average 0.2 0.2
--------------------------------------------------------------------------------------------
2) Abraded skin
--------------------------------------------------------------------------------------------
Rabbit number 24 hour 72 hour
A-B A-B
---------------------------------------------------------------------------------------------
8410 0-0 0-0
8411 0-0 0-0
8412 0-0 0-0
8413 0-0 0-0
8414 0-0 0-0
8415 0-0 0-0
--------------------------------------------------------------------------------------------
Average 0.0 0.0
--------------------------------------------------------------------------------------------
A – erythema; B – edema
Overall, the test material caused slight erythema in 2 of the 12 rabbits (one - 24 hours after application, and the other - 72 hours after application). Conclusion: Due to the slight character of the observed effects the test substance does not have to be classified according to the criteria of the DSD and the CLP regulation.
Individual and average skin reaction scores
1) Intact skin
--------------------------------------------------------------------------------------------
Rabbit number 24 hour 72 hour
A-B A-B
---------------------------------------------------------------------------------------------
8416 0-0 0-0
8417 0-0 0-0
8418 1-0 0-0
8419 0-0 0-0
8420 1-0 0-0
8421 0-0 0-0
--------------------------------------------------------------------------------------------
Average 0.3 0.0
--------------------------------------------------------------------------------------------
2) Abraded skin
--------------------------------------------------------------------------------------------
Rabbit number 24 hour 72 hour
A-B A-B
---------------------------------------------------------------------------------------------
8410 0-0 0-0
8411 0-0 0-0
8412 0-0 0-0
8413 0-0 0-0
8414 0-0 0-0
8415 0-0 0-0
--------------------------------------------------------------------------------------------
Average 0.0 0.0
--------------------------------------------------------------------------------------------
A – erythema; B – edema
Overall, the test material caused slight erythema in 2 of the 12 rabbits 24 hours after application. No sign of skin irritation was observed at 72 hours.
Supporting studies:
- no dermal irritation for CAS 21645-51-2 and 10043-01-3, irritation effects for CAS 7446-70-0 and 13473-90-0 in three animal species after repeated exposure (supporting, source, RA-A, 21645-51-2, Landsdown ABG, 1973)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- other: FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) Draize and Kelly (Drug Cosmet. Industr. 71 (1952) 36)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Test animals:
Species and strain: New Zealand White albino rabbits
Sex: No information
Source: No information
Age at study initiation: No information
Body weight range at the beginning of the study: No information.
Body weight range at the end of study: No information
Data of receipt: No information
Acclimation: No information
Identification: No information
Environmental/housing and feeding conditions:
Lighting period: No information
Temperature: No information
Relative humidity: No information
Housing/Enrichment: “The animals are caged individually and receive no hay or other extraneous material that might enter the eye.”
Ventilation: No information
Feeding conditions
No information - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The untreated eye served as the control.
- Amount / concentration applied:
- 100 mg of the test substance was allowed to “fall on the averted lower lid of one eye.” The eyelids were held together for at least one second to prevent loss of the test material.
- Duration of treatment / exposure:
- The eyes were not washed following instillation. As no examination was conducted at 1 hour after instillation, it is unclear whether the test material was removed from the eye by physiological mechanisms at that time
- Observation period (in vivo):
- Animals were examined 24, 48, 72 hours and 7 days after instillation.
Initial pain reaction was not reported
Clinical signs of toxicity during the study were not reported.
Ocular reactions, read using a binocular magnifying glass, of the individual animals were recorded at each observation time
“The diagnosis of corneal damage is confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers.” [As no animals exhibited signs of cornea damage, this technique, most probably, was not applied] - Number of animals or in vitro replicates:
- 6 animals
- Details on study design:
- SCORING SYSTEM: The FDA scoring scale was used
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- 6/6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- 6/6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- 6/6
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- other: 5/6 animals redness was reversible after 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritant / corrosive response data:
- Initial pain reaction – no information
1 hour after instillation – no examination was conducted
24 hours after instillation: conjunctival redness (score 1) and chemosis (score 1) was observed in all animals. No cornea or iris lesions in any animal.
48 hours after instillation: conjunctival redness (score 1) was observed in all animals and chemosis (score 1) – in 4 animals. No animals showed signs of cornea or iris lesions
72 hours after instillation: conjunctival redness (score 1) was observed in all animals. No animal showed signs of chemosis, cornea or iris lesions.
7 days after instillation: conjunctival redness (score 1) was observed in one animal, and there were no signs of chemosis, cornea or iris lesions in any animal.
Symptoms in the control eye – no information - Other effects:
- Mortality: no mortality was observed during the study period
Body weight: no information
Clinical observation/General Daily Examination: no information - Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- No eye irritation/ corrosion effects were observed. According to the FDA standards applied, aluminium oxide is not considered an eye irritant.
- Executive summary:
An eye irritation study of the test item Aluminium oxide (coded AK 43/79) was performed inWhite albino rabbits. Six animals were used in this experiment. The irritation effects of the test item were evaluated according to theFDA criteria. 100 mg of the test item was administered as a single dose. The test item was placed into the conjunctival sac of the eye. The untreated eye served as control. The eyes of the test animals were not washed after the application of the test item. The eyes were examined 24, 48, 72 hours and 7 days after the application. No examination was conducted 1 hour after the application. Initial Pain Reaction was not reported.
At 24 hours after instillation a conjunctival redness (score 1) and chemosis (score 1) was observed in all animals. No cornea or iris lesions in any animal. At 48 hours after instillation,conjunctival redness (score 1) was observed in all animals and chemosis (score 1) in 4 animals. No animals showed signs of cornea or iris lesions. At 72 hours after instillation,conjunctival redness (score 1) was observed in all animals. No animal showed signs of chemosis, cornea or iris lesions. At 7 days after instillation,conjunctival redness (score 1) was observed in one animal, and there were no signs of chemosis, cornea or iris lesions in any animal.
No information was provided on symptoms in the control eye. No information was provided on animal behaviour, clinical signs of toxicity, or body weight changes during the study period. The observed changes of grade 1 were not considered positive according to the FDA standards applied in this study.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- : observations ought to be made at 1 hour post-application.
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
Sex: not reported
Age: not reported
Weight: 2.2 – 2.6 kg
Environmental/Housing conditions
No information provided.
Feeding conditions
No information provided. - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The right eyes of the animals were used as controls.
- Amount / concentration applied:
- Single application of 100mg solid ALON
- Duration of treatment / exposure:
- no data
- Observation period (in vivo):
- Observations were made at 24, 48, 72 hours and also on days 4 and 7.
- Number of animals or in vitro replicates:
- 9 animals
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): In three animals, the compound was washed out after 2 seconds, in three animals it was washed out after 4 seconds and in 3 animals the substance was not washed out. Tap water was used for washing the animals’ eyes.
SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: fluorescein (2% on day 7) - Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Remarks:
- unwashed
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Remarks:
- unwashed
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Remarks:
- unwashed
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Remarks:
- washed after 2 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Remarks:
- washed after 2 sec
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Remarks:
- washed after 2 sec
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 4 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of 3 animals; unwashed
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 2 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 4 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- of 3 animals; unwashed
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 2 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 4 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- of 3 animals; unwashed
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 2 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- of 3 animals; washed after 4 sec
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Other effects:
- The authors reported no principal toxic effects.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The results from this study were negative and would not support classification of ALON for eye irritation.
- Executive summary:
ALON, a high surface area fumed alumina, was tested for acute eye irritation in 9white rabbits (weights 2.2-2.6 kg) (Cabot, 1969). A single application of 100mg of the powdered substance was applied to the conjunctival sac of the left eye of each animal. In three animals, tap water was used to wash the eye after 2 seconds, in three animals washing occurred after 4 seconds, and in the remaining 3 animals, the test substances was not washed from the eyes. This deviates from OECD TG#405 which recommends washing of a solid substance from the eye if it has not been removed by physiological mechanisms 1 hour after administration. Observations were made at 24 hours, 28 hours, 72 hours, 4 days and 7 days post-application. The untreated eyes of the animals served as controls. The animals’ corneas were also examined using fluorescein stain prior to application and at 7 days to assess corneal damage. Eye irritative effects were scored and graded according to Draize (1959). The only effects reported were at 24 hours post-application: slight erythema (score=1) in all unwashed eyes and two eyes washed after 2 seconds. The erythema had resolved by the 48 hour observation time. Examination of the cornea using the fluorescein stain produced no evidence of damage. The results from this study are negative and a Klimisch Score of 2 is considered appropriate.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- other: FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) Draize and Kelly (Drug Cosmet. Industr. 71 (1952) 36)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Sex: No information
Source: No information
Age at study initiation: No information
Body weight range at the beginning of the study: No information.
Body weight range at the end of study: No information
Date of receipt: No information
Acclimation: No information
Identification: No information
Environmental/Housing conditions
Lighting period: No information
Temperature: No information
Relative humidity: No information
Housing/Enrichment: “The animals are caged individually and receive no hay or other extraneous material that might enter the eye.”
Ventilation: No information
Feeding conditions
No information - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The untreated eye served as the control.
- Amount / concentration applied:
- 100 mg of the test substance was allowed to “fall on the averted lower lid of one eye.” The eyelids were held together for at least one second to prevent loss of the test material.
- Duration of treatment / exposure:
- The eyes were not washed following instillation. As no examination was conducted at 1 hour after instillation, it is unclear whether the test material was removed from the eye by physiological mechanisms at that time
- Observation period (in vivo):
- Animals examined 24, 48, 72 hours and 7 days after instillation.
Initial pain reaction was not reported
Clinical signs of toxicity during the study were not reported.
Ocular reactions of individual animals were recorded at each observation time
Ocular reactions were read using a binocular magnifying glass.
“The diagnosis of corneal damage is confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers.” [As no animals exhibited signs of cornea damage, this technique, most probably, was not applied] - Number of animals or in vitro replicates:
- 6 animals
- Details on study design:
- SCORING SYSTEM: The FDA scoring scale was used
TOOL USED TO ASSESS SCORE: biomicroscope - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- 6/6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- 6/6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 3
- Reversibility:
- not fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- chemosis score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritant / corrosive response data:
- Initial pain reaction – no information
1 hour after instillation – no examination was conducted
24 hours after instillation: conjunctival redness score 1 was observed in 5 animals, conjunctival redness score 2 – in 1 animal, and chemosis (score 1) - in 3 animals. No cornea or iris lesions were observed in any animal.
48 hours after instillation: conjunctival redness (score 1) was observed in all animals and chemosis (score 1) – in 2 animals. No animals showed signs of cornea or iris lesions
72 hours after instillation: conjunctival redness (score 1) was observed in all animals. No animal showed signs of chemosis, cornea or iris lesions.
7 days after instillation: conjunctival redness (score 1) was observed in 2 animals; there were no signs of chemosis, cornea or iris lesions in any animal.
Symptoms in the control eye – no information - Other effects:
- Mortality
No mortality was observed during the study period
Body weight
No information
Clinical observation/General Daily Examination
No information - Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- No eye irritation/ corrosion effects were observed. According to the FDA standards applied, aluminium oxide is not considered an eye irritant.
- Executive summary:
An eye irritation study of the test item Aluminium oxide (coded AK 44/79) was performed in White albino rabbits. Six animals were used in this experiment. The irritation effects of the test item were evaluated according to the FDA criteria. 100 mg of the test item was administered as a single dose into the conjunctival sac of the eye. The untreated eye served as control. The eyes of the test animals were not washed after the application of the test item. The eyes were examined 24, 48, 72 hours and 7 days after the application. No examination was conducted 1 hour after the application. The Initial Pain Reaction was not reported.
At 24 hours after instillation a conjunctival redness score 1 was observed in 5 animals, conjunctival redness score 2 in 1 animal, and chemosis (score 1) in 3 animals. No cornea or iris lesions were observed in any animal. At 48 hours after instillation, conjunctival redness (score 1) was observed in all animals and chemosis (score 1) in 2 animals. No animals showed signs of cornea or iris lesions. At 72 hours after instillation,conjunctival redness (score 1) was observed in all animals. No animal showed signs of chemosis, cornea or iris lesions. At 7 days after instillation, conjunctival redness (score 1) was observed in 2 animals; there were no signs of chemosis, cornea or iris lesions in any animal.
No information was provided on symptoms in the control eye. No information was provided on animal behaviour, clinical signs of toxicity, or body weight changes during the study period. The changes of observed in this study were not considered positive according to the FDA standards applied.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Justification for type of information:
- Refer to analogue justification provided in IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- of 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: supporting, source, RA-A, 21645-51-2, LAB Research, 2009
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
- Conclusions:
- The source substance (CAS 21645-51-2) is not considered as irritating to the eye. Applying the read-across approach, the target substance (CAS 1344-28-1) is expected to have a similar eye irritation/ damaging potential.
Referenceopen allclose all
Individual
scores awarded to the ocular lesions elicited by AK 43/79
--------------------------------------------------------------------------------------------------------------
Conjunctivae
Rabbit
----------------------------------
number cornea iris redness chemosis
------------------------------------------------------------------------------------------------------------------
After 24 hours
1 0 0 1 1
2 0 0 1 1
3 0 0 1 1
4 0 0 1 1
5 0 0 1 1
6 0 0 1 1
After 48 hours
1 0 0 1 0
2 0 0 1 1
3 0 0 1 1
4 0 0 1 0
5 0 0 1 1
6 0 0 1 1
After 72 hours
1 0 0 1 0
2 0 0 1 0
3 0 0 1 0
4 0 0 1 0
5 0 0 1 0
6 0 0 1 0
After 7 days
1 0 0 0 0
2 0 0 0 0
3 0 0 0 0
4 0 0 0 0
5 0 0 0 0
6 0 0 1 0
Individual results were provided in the report for each rabbit.
The total scores are provided in the table below for the different observation times:
Rabbit # |
Washing |
24 hrs
|
48 hrs |
72 hrs |
4 days |
7 days |
Fluor-escein (t=0) |
Fluor-escein (t=7d) |
68-2816 |
unwashed |
2 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2817 |
unwashed |
2 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2818 |
unwashed |
2 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2819 |
washed-2s |
0 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2820 |
washed-2s |
2 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2821 |
washed-2s |
2 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2822 |
washed-4s |
0 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2823 |
washed-4s |
0 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
69-2824 |
washed-4s |
0 |
0 |
0 |
0 |
0 |
Neg. |
Neg. |
|
|
|
|
|
|
|
|
|
The total scores of 2 at 24 hours in all unwashed eyes and in treated eyes of two animals with washing after 2 seconds result from slight conjunctival erythema (scored as 1). The slight erythema had resolved by 48 hours in all animals. No other effects were observed. There was no evidence of corneal damage using fluorescein stain at baseline or at 7 days in any animal.
Individual scores awarded to the ocular lesions elicited by AK 43/79 After 24 hours 1 0 0 1 1 2 0 0 1 0 3 0 0 1 0 4 0 0 1 0 5 0 0 1 1 6 0 0 2 1 After 48 hours 1 0 0 1 0 2 0 0 1 0 3 0 0 1 0 4 0 0 1 0 5 0 0 1 1 6 0 0 1 1 After 72 hours 1 0 0 1 0 2 0 0 1 0 3 0 0 1 0 4 0 0 1 0 5 0 0 1 0 6 0 0 1 0 After 7 days 1 0 0 0 0 2 0 0 1 0 3 0 0 0 0 4 0 0 0 0 5 0 0 0 0 6 0 0 1 0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Skin irritation:
No human studies were located that examined acute dermal irritation/corrosion effects in workers exposed occupationally to aluminium oxide particulates. Animal studies conducted by Degussa (1979a,b) reported negative results for acute dermal irritation. An animal study that exposed rabbits to aluminium oxide powder in accordance with OECD TG 404 “Acute Dermal Irritation/Corrosion” (1989) provides evidence supporting the absence of dermal irritation effects of aluminium oxide (Aluminium oxide, IUCLID, 2000). A full report of this study is not available.
A pre-guideline study conducted by Cabot (Cabot, 1969a) on Al2O3, a high purity fumed alumina formed by the chemical hydrolysis of aluminium chloride, also reported negative results and contributes to the weight of evidence. The negative results from the LAB Research Ltd. Study (2009) and Lansdown (1973) for aluminium hydroxide also contribute to the weight of evidence that irritative properties of aluminium oxide are unlikely on acute dermal exposure. A detailed rationale and justification for the analogue read-across approach is provided in the technical dossier (see IUCLID section 13.2).
A study investigated dermal irritation effects of aluminium oxide in New Zealand White albino rabbits equivalent to OECD 404 is available (Degussa, 1979a). 0.5 g of the test substance was placed on the intact or abraded skin of the rabbits under a surgical patch measuring 2.5 Χ 2.5 cm. Six rabbits had intact skin and six rabbits abraded skin. The exposure continued for 24 hours (a 4 hour exposure is recommended by OECD 404), and skin lesions were scored immediately after patch removal and 48 hours later (24 and 72 hours after the application of the test material). Two sets of scoring criteria were used: Draize (1944) - 24 hours after the material application and CIVO - 72 hours after the application.
Slight erythema was observed on the intact skin of 2 animals (one 24 hours after the substance application and the other 72 hours after application). No signs of skin irritation were observed on the abraded skin at any time. The overall primary irritation score from the study (0.2) would not lead to classification.
Another study conducted for Degussa corporation investigated dermal irritation effects of aluminium oxide in New ZealandWhite albino rabbits (Degussa, 1979b). 0.5 g of the test substance was placed on the intact or abraded skin of the rabbits under a surgical patch measuring 2.5Χ2.5 cm.Six rabbits had intact skin and six rabbits had abraded skin. The exposure continued for 24 hours (4 hour exposure is recommended by OECD 404), and skin lesions were scored immediately after patch removal and 48 later (24 and 72 hours after the application of the test material). Two sets of scoring criteria were used: Draize (1944) - 24 hours after the material application and CIVO - 72 hours after the application.
Slight erythema was observed on the intact skin of 2 animals 24 hours after the substance application. No signs of skin irritation were seen at 72 hours.No signs of skin irritation were observed on the abraded skin at any time. The overall primary irritation score from the study (0.3 at 24 hours) would not lead to classification.
A study conducted at Hazleton Laboratories Inc. for the Cabot Corporation investigated dermal irritation effects of a high purity fumed alumina produced by the chemical hydrolysis of aluminium chloride in New Zealand White rabbits (Cabot, 1969a). 0.5 g of the substance in 1.0 mL of distilled water was applied to pre-moistened skin on the backs of 6 rabbits under gauze patches. Three of the rabbits had abraded skin and three intact skins. The patches remained place for 24 hours. Lesions were scored at 24 hours and at 72 hours using the scoring criteria of Draize (1959). The report lacks detail on animal husbandry and signs of toxicity. Further details of the test substance characteristics were obtained from the study sponsor. The results showed slight erythema in all three rabbits with abraded skin at 24 hours. The erythema had resolved by 72 hours. No erythema was observed in the animals with intact skin. No animal exhibited edema. The overall primary irritation score from the study (0.25) would not lead to classification.
Aluminium hydroxide (SH-20 Muster) was tested in a primary dermal irritation study in New Zealand White rabbits (Lab Research Ltd., 2009). Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method OECD No.: 404, 2002).
The test item was administered as supplied, at a single dose of 0.5 g. Gauze was placed onto the hairless skin of the rabbit, test item was applied to the gauze, additional gauze was placed over the test item and an adhesive clear plastic patch applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.
After 4 hours, the remaining test item was removed with water at body temperature. To assess skin irritation, animals were examined at 1, 24, 48 and 72 hours after the patch removal. Additional general examinations were performed daily. There was no mortality or systemic clinical changes related to Aluminium Hydroxide administration. There was no effect of treatment on body weight. At observation one hour after patch removal, very slight erythema (score 1) was observed in two animals. At 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals. As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.
The animals’ individual means scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively.
Results from Lansdown (1973), a non-guideline study, indicate that repeated exposure (5 daily administrations) of a 10% aluminium hydroxide suspension did not lead to dermal irritation under the experimental conditions. Lansdown (1973) studied the irritation effects and epidermal damage on mammalian skin (mice, rabbits and pigs) from contact exposure to six aluminium salts at concentrations ranging from 2.5% to 25%. Macroscopic (erythema, thickening and scaling), microscopic pathological (stained thin-sections) and histochemical examinations were carried out. Effects were described in relation to pH and the deposition of aluminium in the stratum corneum. Aluminium hydroxide, chloride (anhydrous), sulphate, nitrate, and basic acetate with minimum purity of 97% were applied to 2 cm² areas of shaved skin on the back of mice (TF strain, n=5) and New Zealand white Norfolk rabbits (n=3), and to 4 cm² areas of shaved skin on the back of pigs (large white strain, n=2) for 5 days. Distilled water was used as a negative control. Aluminium hydroxide (pH 7.2) was applied as a 10% suspension in 0.2% Tween-80. The author reported that previous studies had shown that Tween-80 was not an irritant to mouse skin when applied repeatedly at a concentration of 2.5% (Lansdown & Grasso, 1972).
Positive results were observed for aluminium chloride and aluminium nitrate. Aluminium hydroxide, and the other salts used, did not cause any visual or microscopic irritation effects or lead to inflammatory effects on the skin of mice, rabbits or pigs. No accumulation of aluminium was observed in the epidermis after application of aluminium hydroxide. Irritation effects on application of aluminium chloride (administered at concentrations of 25%, 10%, 5% and 2.5%) were concentration-dependent and related to the amount of metal ion bound to the skin and the resulting denaturation of epidermal keratin. The pathological changes in the skin of mice treated with 25% aluminium chloride include pronounced epidermal hyperkeratosis, acanthosis with marked inter- and intra-cellular oedema and microabscess formation in the epidermis. Positive irritative effects were observed for aluminium chloride and aluminium nitrate, the two solutions that had the lowest pH values, 2.3 and 2.4, respectively. Results from solutions of hydrochloric acid and Universal buffer showed that the low pH was not the cause of irritative effects. The low pH may however have led to increased deposition of aluminium in the epidermal keratin. The histochemical results suggest that aluminium may cause denaturation of epidermal keratin. For local effects, the possible toxicity of the counter-ions, chloride and nitrate, also require consideration. The study contributes to the weight of evidence for a dermal irritative potential for aluminium if deposited in the keratin. Aluminium hydroxide, due to its insolubility, did not lead to irritative effects.
Additional information:
Verbeken et al.(2011) discussed the results of the evaluation of the potential migration of Al and other metals (arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb)) from food-grade Al foil used for human skin allograft cryo preservation at the Queen Astrid Military Hospital, Belgium. The hospital skin bank has employed food-grade Al foil in preservation of donor skin beginning in 1924 and since then it has been used in treatment of burns and ulcers. The non-toxic properties reported by Johns (1949) and Hambury (1957) and the absence of sensitivity reactions in humans (Hambury, 1957) are among the advantages of the Al foil dressings described. Poole et al. (1979) found no significant increase in serum or plasma Al levels in patients in whom sterilized food-grade Al foil was used as a temporary wound dressing. Those data indicate low transcutaneous Al bioavailability through burned, damaged or otherwise injured skin. It should be noted here that, at present, these publications are not available but have been requested through Interlibrary loan, University of Ottawa.
Measurements of Al in the pooled cryo preservation medium of seven donor skin samples that had been stored for 10 years detected 1.4 mg Al/L using inductively coupled plasma atomic emission spectrometry (ICP-AES).The method detection limit was 100 µg Al/L. Aluminium, arsenic and lead were not detected in 10 donor skin samples using graphite furnace atomic absorption spectrometry (GFAAS), whereas Cd was detected in 4/10 skin samples (0.001 to 0.045 mg/L) and total Cr was detected in 8/10 skin samples (0.0016 to 0.0242 mg/L). It should be noted that Cr was also detected in the analytical blank at 0.0042 mg/L. Retrospective analyses revealed no adverse reactions (e.g., irritation, hypersensitive reactions or other clinical signs of intoxication) among graft recipients that could be related to the possible presence of Al or other metals in the grafts. Histological analysis revealed no differences between the cryo preserved donor skin samples and fresh skin following blind comparisons of the structural integrity of fresh and preserved skin conducted by an experienced dermato-pathologist. The parameters included evaluation of pigmentation, presence and integrity of hair follicles and their associated muscles, sweat and sebaceous glands and integrity of the dermal-epidermal junction. The presence of apoptotic and/or necrotic cells, sentinels of local tissue stress and signs of inflammation, were also included. It should be noted that this evaluation was conducted on cryo preserved skin (30% (v/v) glycerol in physiological water) that was stored in vapor phase liquid nitrogen (≤ 135 °C).
Overall, Verbeken et al. (2011) provide indirect evidence based on historical experience that aluminium metal/aluminium oxide (present in Al foil) did not cause adverse reactions (e.g., irritation, hypersensitivity) on injured human skin. A Klimisch Score of 4 (not assignable) was considered appropriate for this study.
Mayeux et al. (2012) inspected deposition patterns of aluminium chloride in the stratum corneum (SC) harvested by cyanoacrylate skin surface strippings (CSSS) following one or seven days application of aqueous 5% AlCl3 on the forearms of volunteers. While the study did not give direct information on local irritation, it did indicate low irritancy from the investigations on the CSSS. The study was performed in accordance with the Declaration of Helsinki. A total of 37 volunteers of both genders (aged 21–59 years) participated in the study (no other details available). The AlCl3solution was applied on the normal skin of the volar aspect of the forearm (no other details were available). After air drying, biometrological measurements were performed at rest and after a moderate 10-min physical exercise on a cycloergometer. The AlCl3-treated skin was observed using two ultraviolet light-emitting cameras to record subtle variations or changes related to AlCl3deposition and /or local effects. After a single application of AlCl3, Al deposits on skin were observed predominantly inside the microrelief lines and at their crossings. After daily applications of AlCl3 for 1 week, Al deposits were evident within the plateaus delimited by the microrelief lines. No information regarding local irritation following single or repeated applications of AlCl3or after physical exercise compared with the rest condition was provided.
In addition, the corneoxenometry bioassay to predict local AlCl3 irritation was conducted (Goffin et al., 2000; Pie´rard-Franchimont et al., 2010). Briefly, CSSS were dipped into AlCl3solutions at 5, 20 and 40% for 2 h and these samples were then dried and stained with toluidine blue and basic fuchsin for 3 min. After rinsing, the color of the samples was measured and the staining intensity of the SC was calculated. No significant differences in the median or range of staining intensity were detected at any concentration compared to the concurrent water control. The authors suggested these data were indicative of low irritancy potential for AlCl3 under the conditions of their study.
Among the limitations of this study are: little information was available on the study participants, test compound (chemical characteristics and purity), no information regarding pH of the administered AlCl3 solutions or the pH of the skin after exposure and the report provided no details on the application technique (e.g. duration of contact, occlusion condition, etc.) A Klimisch Score of 3 (not reliable) has been assigned to this study (mechanism of action study).
The Mayeux et al. (2012) results are in accord with results by Flarend et al. (2001) who studied the systemic uptake of Al in humans under a “worst case scenario” with occlusive conditions and possibly irritated skin from an aluminium chlorhydrate-containing antiperspirant using 26Al as a tracer. The study was carried out with two volunteers, one male and one female. The female subject developed local irritation to the adhesive bandages used for occlusion. Based on urine and blood measurements, dermal absorption of aluminium chlorhydrate was low - only 0.01% of the applied Al dose was absorbed. Lansdown (1973) observed local irritation and epidermal damage in mice, rabbits and pigs after 5 days exposure to AlCl3. The irritation seen after repeated topical application of AlCl3 at 2.5, 5, 10 or 25% was concentration-dependent and it was related to the amount of Al ion bound to the skin and resulting denaturation of epidermal keratin. The variations in the results between human and animal studies might be attributed in part to different types of test material, differences between animal and human skin, the concentrations and pH of the test materials and overall designs of these studies.
Yanagishita et al. (2011) investigated histological localization of Al after topical AlCl3 treatment for palmar hyperhidrosis. The mechanism of the antiperspirant action of AlCl3 was evaluated in 127 patients with palmar hyperhidrosis (no other details available) who received a topical 20% solution without occlusion daily (once a day) for 1 month. No mention was made whether any of the participants complained of local irritation or other clinical signs following prolonged treatment with AlCl3. Wooley-Lloyd and Valins (2009) (as described in Yanagishita et al., 2011) investigated topical exposure to aluminium chloride hexahydrate in a salicylic acid gel as a novel agent for treatment of hyperhidrosis. These authors indicated that treatment-relevant adverse effects were associated with local irritation with transient itching. However, it should be noted that the action of topical antiperspirants depends primarily on the specific active ingredients (aluminium salts, non-ionic agents and ionic agents) (Quatrale, 1985). The findings reported by Yanagishita et al. (2011) are inadequate to evaluate the irritant potential on skin of the aluminium compounds under review.
Overall, the weight of evidence suggests that aluminium oxide dust or powder is unlikely to lead to irritative effects on acute dermal exposure.
Eye irritation:
An animal study conducted according to OECD TG #405 “Acute Eye Irritation/Corrosion” (1989) has provided data supporting the absence of irritation effects of aluminium oxide (Aluminium oxide, IUCLID, 2000). However, the full report of this study is not available. Studies by Degussa (1979a,b) on aluminium oxide and a study by Cabot (1969) on a fumed alumina, also reported negative results. The negative results from the LAB Research Ltd. Study (2009) on aluminium hydroxide also contribute to the weight of evidence for a lack of irritative properties of aluminium oxide on acute eye exposure. A detailed rationale and justification for the analogue read-across approach is provided in the technical dossier (see IUCLID section 13.2).
An eye irritation study of the test item Aluminium oxide (coded AK 43/79) was performed in White albino rabbits (Degussa, 1979). Six animals were used in this experiment. The irritation effects of the test item were evaluated according to the FDA criteria. 100 mg of the test item was administered as a single dose. The test item was placed into the conjunctival sac of the eye. The untreated eye served as control. The eyes of the test animals were not washed after the application of the test item. The eyes were examined 24, 48, 72 hours and 7 days after the application. No examination was conducted 1 hour after the application. Initial Pain Reaction was not reported. At 24 hours after instillation a conjunctival redness (score 1) and chemosis (score 1) was observed in all animals. No cornea or iris lesions in any animal. At 48 hours after instillation, conjunctival redness (score 1) was observed in all animals and chemosis (score 1) in 4 animals. No animals showed signs of cornea or iris lesions. At 72 hours after instillation, conjunctival redness (score 1) was observed in all animals. No animal showed signs of chemosis, cornea or iris lesions. At 7 days after instillation, conjunctival redness (score 1) was observed in one animal, and there were no signs of chemosis, cornea or iris lesions in any animal.
No information was provided on symptoms in the control eye. No information was provided on animal behaviour, clinical signs of toxicity, or body weight changes during the study period. The observed changes of grade 1 were not considered positive according to the FDA standards applied in this study.
ALON, a high surface area fumed alumina, was tested for acute eye irritation in 9white rabbits (weights 2.2-2.6 kg) (Cabot, 1969). A single application of 100mg of the powdered substance was applied to the conjunctival sac of the left eye of each animal. In three animals, tap water was used to wash the eye after 2 seconds, in three animals washing occurred after 4 seconds, and in the remaining 3 animals, the test substances was not washed from the eyes. This deviates from OECD TG#405 which recommends washing of a solid substance from the eye if it has not been removed by physiological mechanisms 1 hour after administration. Observations were made at 24 hours, 28 hours, 72 hours, 4 days and 7 days post-application. The untreated eyes of the animals served as controls. The animals’ corneas were also examined using fluorescein stain prior to application and at 7 days to assess corneal damage. Eye irritative effects were scored and graded according to Draize (1959). The only effects reported were at 24 hours post-application: slight erythema (score=1) in all unwashed eyes and two eyes washed after 2 seconds. The erythema had resolved by the 48 hour observation time. Examination of the cornea using the fluorescein stain produced no evidence of damage. The results from this study are negative and a Klimisch Score of 2 is considered appropriate.
An acute eye irritation study of the test item Aluminium Hydroxide was performed in New Zealand White rabbits.The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002). The test item was placed into the conjunctival sac of the left eye of each animal.The untreated right eye served as control. An amount of the test item was administered as a single dose.The eyes of the test animals were washed out at one hour after the application of the test item. The eyes were examined at 1, 24, 48, 72 hours after the application. Initial Pain Reaction (IPR) (score 1) was observed in two animals, IPR (score 2) in one animal. One hour after the application, conjunctival redness (score 2) was observed in all animals, conjunctival discharge (score 2) in one and conjunctival discharge (score 1) was found in two animals. At 24 hours after treatment: two animals showed slight redness (score 1). At 48 hours after treatment: full recovery was observed. At 72 hours after treatment: there were no clinical signs observed.
An eye irritation study of the test item aluminium oxide was performed in White albino rabbits. Six animals were used in this experiment (Degussa, 1979). The irritation effects of the test item were evaluated according to the FDA criteria. 100 mg of the test item was administered as a single dose into the conjunctival sac of the eye. The untreated eye served as control. The eyes of the test animals were not washed after the application of the test item. The eyes were examined 24, 48, 72 hours and 7 days after the application. No examination was conducted 1 hour after the application. The Initial Pain Reaction was not reported. At 24 hours after instillation a conjunctival redness score 1 was observed in 5 animals, conjunctival redness score 2 in 1 animal, and chemosis (score 1) in 3 animals. No cornea or iris lesions were observed in any animal. At 48 hours after instillation, conjunctival redness (score 1) was observed in all animals and chemosis (score 1) in 2 animals. No animals showed signs of cornea or iris lesions. At 72 hours after instillation,conjunctival redness (score 1) was observed in all animals. No animal showed signs of chemosis, cornea or iris lesions. At 7 days after instillation, conjunctival redness (score 1) was observed in 2 animals; there were no signs of chemosis, cornea or iris lesions in any animal. No information was provided on symptoms in the control eye. No information was provided on animal behaviour, clinical signs of toxicity, or body weight changes during the study period. The changes of observed in this study were not considered positive according to the FDA standards applied.
Overall, the weight of evidence suggests a lack of chemical irritative properties for aluminium oxide dust on acute eye exposure.
Respiratory irritation:
Human Studies
Results from two studies that examined cross-shift lung effects among aluminium reduction workers (Chan-Yeung et al., 1983; Kilburn and Warshaw, 1989) provide insufficient evidence for an acute, irritative, substance-specific effect from inhalation of aluminium oxide particulates in this occupational setting.
Airborne exposures in the potroom are multiple – several of which may contribute to a pulmonary response. The evidence suggests a role for aluminium fluoride (AlF3), cryolite
(Na4AlF6), or hydrogen fluoride (HF) in the causation of observed lung effects (ATSDR, 2008; Krewski et al., 2007; Sorgdrager et al., 1995; Soyseth and Kongerud, 1992; Kongerud, 1992). Co-exposure to nickel and the extremely high, accidental exposure levels cannot be excluded as contributory to the toxic pneumonia and fibrosis found in a thermal sprayer (20% aluminium and 80% nickel metal content; Schaller et al., 2007). Results from three studies that examined cross-shift lung effects among aluminium-exposed welders (Kilburn et al., 1989; Fishwick et al., 2004; Gube et al., 2009) provide insufficient evidence for an acute, irritative, substance-specific effect from inhalation of aluminium oxide fume.
No studies were located that reported acute lung effects in workers from short-term inhalation exposure to aluminium hydroxide dust. Results from cross-sectional studies among bauxite-exposed workers are inconclusive concerning a respiratory irritative effect associated with the cumulative exposure levels encountered in the workplace (Beach et al., 2001; Fritschi et al. 2001/2003; Townsend et al., 1985, 1988). Threats to the validity of the available studies include possible selection biases due to cross-sectional designs, residual confounding by smoking, possibly irritative co-exposures, and the lack of measurements of the respirable fraction.
Animal Studies
Pauluhn (2009a) observed an inflammatory response in BALF cytology and biochemistry that was mild and to some degree reversible in a subacute study in rats exposed by inhalation to agglomerated nano-sized aluminium oxyhydroxide particulates. The inflammatory response after 10 days of exposure was significant at the highest dose of 28 mg/m³ but was not detectable at 0.4 and 3 mg/m³. Lindenschmidt et al. (1990) administered single doses of 10 and 50 mg/kg bw Al2O3 to Fischer 344 rats by intratracheal instillation (ITI). Responses to crystalline silica and TiO2 were also examined and compared with a saline control. At 50 mg/kg bw, both Al2O3 and TiO2 exhibited early changes in BAL biochemistry and cells consistent with a mild inflammatory response. All values returned to baseline by 9 weeks post-treatment. For the 10 mg/kg bw level, values had returned to normal 2 weeks post-treatment. Tornling et al. (1993) compared BAL biochemistry in Sprague-Dawley rats on single intratracheal instillation of primary or secondary alumina. Only the fluoride-containing secondary alumina exhibited a reversible, short-term inflammatory response. Fibronectin was elevated in both the primary and secondary alumina-treated groups at the end of the study suggesting a role of the alumina component in the development oflonger-term effects. White et al. (1987) compared BAL biochemistry, BAL cell counts, and lung tissue biochemistry in male Fischer 344 rats exposed to virginal alumina or potroom dust in a short-term, single ITI dose study. The effects of the alumina were typical of a nuisance dust with no evidence of an acute inflammatory response.
Thomson et al. (1986) conducted a study in male Fischer 344 rats (10-12 weeks old) to investigate and compare the acute inhalation toxicity of aluminium flake and brass flake dusts. Both were irregularly shaped flake dusts coated with < 2% palmitic and stearic acids to facilitate the milling process in manufacture. Two experiments were conducted: one with observations at 24 hours and 14 days post-exposure, the other with additional groups observed at 3 and 6 months post-exposure, in order to examine longer term effects of the acute exposure. The animals were exposed to the dust for 4 hours. During the exposure period, the animals were placed in compartmentalized wire cages without food, water or bedding in temperature - (22 °C ± 2 ºC) and humidity - (30 to 70%) controlled chambers. The test atmospheres were produced using a Metronics Model #3 aerosol generator. Nominal concentrations for the aluminium powder were 10, 50, 100, 200 and 1000 mg/m³. The corresponding concentrations determined gravimetrically were 9.16, 47.3, 111, 206 and 888 mg/m³. The MMAD for the aluminium powder was 1.58µm (geometric mean diameter from microscopic analysis = 2.82 ± 0.26 µm). All animals were examined for toxic signs before and after exposure and daily during the post-exposure period. The animals were weighed at weekly intervals during the experimental and post-exposure periods. Pulmonary function measurements were conducted at 24 hours, 14 days, 3 months and 6 months post-exposure. Bronchopulmonary lavage was conducted and the BALF analysed for total cell counts, differential cell counts, and biochemical parameters (total protein and levels of glucose-6-phosphate dehydrogenase (G-6-PD), lactate dehydrogenase (LDH), and alkaline phosphatase (ALKP)). Blood samples were also collected by cardiac puncture at each timepoint post-exposure for the analysis of copper, zinc, and aluminium. After blood collection, rats were necropsied and the following examinations performed: total body weight, organ weight (heart, lung, kidneys, gonads), gross and microscopic pathology of nasal air passages, trachea, lungs and hilar lymph nodes. No mortality was observed even at the highest aluminium flake concentration. No toxic signs were observed and there were no changes in measurements of lung function even at the highest dose (1000 mg/m³). At concentrations greater than 10 mg/m³, an increase in polymorphonuclear neutrophils in the bronchoalveolar lavage was observed at 24 hours, typical of a mild acute inflammatory response. Increases in lactate dehydrogenase, alkaline phosphatase and total protein that persisted to 3 months provide evidence for a chronic irritant response in the presence of insoluble aluminium flakes retained in the lungs. These changes were not observed at the lowest dose level, 10 mg/m³. Multifocal microgranulomas were observed in terminal airways and alveolar septae in the 200 and 1000 mg/m³ dose groups at 14 days, 3 months and 6 months. Black particulate material was observed in the hilar lymph nodes at 14 days and also later timepoints suggesting clearance by alveolar macrophages. The acute inflammatory response to aluminium flakes was less dramatic than those for more soluble brass dust. The brass dust, however, did not exhibit evidence of a chronic irritant response, effects were resolved by 14 days post-exposure with the exception of larger numbers of alveolar macrophages around terminal airways which had resolved by 3 months. Brass particulate matter was not found in the lavage fluid or in histopathological examinations.
This study provided evidence for a mild, acute inflammatory response in rats on inhalation of stearin-coated aluminium flakes and also for the retention of the insoluble flakes in the lungs resulting in a persistent irritation response at doses greater than 10 mg/m³. Aluminium metal is highly reactive and readily undergoes oxidation to form an inert oxide coat in air. When the aluminium dust or powder comes into contact with air prior to inhalation, exposure does not occur to reactive zero valence aluminium metal but to aluminium oxide. Where a coating such as stearine is present that acts to prevent the oxidation of the metal short-term exposure will be to the aluminium-stearate coating, and not to the aluminium metal. It is technically a challenge to conduct studies to assess the acute exposure to “aluminium metal”. In addition, given the physical hazard associated with fine aluminium powders, to conduct such studies would not be technically feasible.
Based on an assessment of the available data, acute exposure to uncoated “aluminium metal” powder by inhalation will be exposure to aluminium oxide. The study by Thomson et al. (1986) suggests that acute exposure to stearin-coated aluminium flakes does not lead to a persistent response at dose levels of 10 mg/m³ (NOAEC).
Overall, the weight of evidence from human and animal studies does not support a substance-specific acute, respiratory irritative hazard for aluminium dust or powder.
Summary
Overall, the current evidence for an acute irritative effect on inhalation exposure to aluminium oxide or bauxite from human studies does not support a chemical-specific irritative effect. The evidence from animal studies and in-vitro studies also does not support a chemical-specific irritative effect. Based on the available data, aluminium oxide and aluminium hydroxide dust are low cytotoxicity “nuisance dusts” with mild, respiratory irritant effects on acute exposure.
Justification for classification or non-classification
Acute Skin Irritation
Available data are adequate to conclude that there is no need to recommend Classification and Labelling (2008) requirements for skin irritation from acute exposures to aluminium oxide.
Acute Eye Irritation
Available data are adequate to conclude that there is no need to recommend Classification and Labelling (2008) requirements for eye irritation from acute exposures to aluminium oxide dust or powder.
Acute respiratory irritation:
Overall, the current evidence for an acute irritative effect on inhalation exposure to aluminium oxide or bauxite from human studies does not support a chemical-specific irritative effect. The evidence from animal studies and in-vitro studies also does not support a chemical-specific irritative effect.
Overall, according to DSD (67/548/EEC) or CLP (1272/2008/EC)classification criteria for irritation/corrosion, no classification is required.
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