Dialuminium titanium pentaoxide

Endpoint summary

Description of key information

Guideline-compliant studies of eye and skin irritation are available.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5th March 2012 to 15th June 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with relevnat OECD Guidelines and GLP compliance, with no deviations likely to affect the integrity of the study.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan Laboratory Animals Inc.
- Age at study initiation: 18 weeks old.
- Weight at study initiation: 3.25 - 3.7kg
- Housing: Housed individually in aluminium cages (W 360 x D 550 x H 350mm) with wire mesh bottoms.
- Diet (e.g. ad libitum): Free access to RC4 pelletd diet (Oriental Yeast Co., Ltd., Lot numbers 111212 and 120113) ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: Animal for the first application was acclimated for 12 days. Animals in the second application were acclimated for 14 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 5°C
- Humidity (%): 55 ± 25%
- Air changes (per hr): 11 to 14 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours dark and 12 hours light (light period from 07:00 to 19:00)

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g of the test material was moistened with 0.5 mL of water for injection.

Duration of treatment / exposure:

In Application 1, the exposure period for step 1 was 3 minutes, for step 2 was 1 hour and for step 3 was 4 hours. In Application 2, the exposure period was for 4 hours.

Observation period:

The test sites for the 1 and 4 hour exposure periods were examined at 1, 24, 48 and 72 hours after removal of the the test material and the skin irritation/corrosion potential of the test material was determined.

In Application 1, the test site of the test animal used in steps 1 to 3 were observed for effects of skin corrosivity immediately after removal of the test test material. For the 3 minute exposure in Application 1, Step 1, the exposure site was observed at 1 and 24 hours after removal of the application.

Clinical observations were conducted immediately after removal of the test material and again after 1 hour for the test animal used in Step 1 to 3 of Application1.

For the two test animals in Application 2, observations for clinincal signs of toxicity were made immedaitely and at 1, 4 and 5 hours after the test material was applied. The day following application and thereafter, each animal was observed once daily up to the day of final observation (day 3 after application).

All test animals were weighed on the day of application and on the final day of observation.

Number of animals:

First application: 1 animal
Second application: 2 animals.

Details on study design:

TEST SITE
- Area of exposure: Dorsal area of the animal, approximately 2.5 cm x 2.5 cm.
- Type of wrap if used: The test material was applied to a lint patch lined with oil paper. The patch was applied to the application site and covered with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The areas of exposure were wiped with absorbent cotton soaked with water.
- Time after start of exposure: In the first application, for step 1, the test material was removed after 3 minutes exposure, in step 2, the material was removed after 1 hour exposure and in step 3, the material was removed after 4 hours exposure.

In the second application, the treated areas were wiped after 4 hours exposure to the test material.

SCORING SYSTEM: Scored according to Draize Criteria (1959).

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Remarks on result:

other: No effects were observed at any time point, in any animal

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Remarks on result:

other: No effects were observed at any time point, in any animal

Irritant / corrosive response data:

In Application 1, step 1, after 3 minutes exposure, no corrosive change was observed immediately after removal of the test application. No skin reactions including erythema or oedema were observed at 1 or 24 hours after removal of the test material.

In Application 1, step 2, after 1 hour exposure, no corrosive change was observed immedaitely after removal of the test application. No skin reactions including erythema or oedema were observed at 1, 24. 48 or 72 hours after removal of the test material.

In Application 1, step 3, after 4 hours exposure, no corrosive change was observed immedaitely after removal of the test application. No skin reactions including erythema or oedema were observed at 1, 24. 48 or 72 hours after removal of the test material. Individual mean values at 24, 48 and 72 hours after removal of the application was 0.

In Applicaiton 2, step 4, after 4 hours exposure, no corrosive change was observed immedaitely after removal of the test application. No skin reactions including erythema or oedema were observed at 1, 24. 48 or 72 hours after removal of the test material. Individual mean values at 24, 48 and 72 hours after removal of the application was 0 for each animal.

Other effects:

No abnormal clinical signs were observed in any test animal during the observation period.

No abnormalities in body weight gain were observed in any animal during the observation period.

No additional information.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test material, Aluminium titanium oxide was not considered to be irritating or corrosive.

Executive summary:

In a study conducted to determine the potential of aluminium titanium oxide to cause skin irritation or corrosion, a study was conducted in Japanese White rabbits in accordance with OECD Guideline 404 and GLP. There were no signs of irritation or corrosion observed at any of the time-points investigated.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 5th, 2012 to June 15th, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with GLP and the applicable OECD guideline with no deviations.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Japan Laboratory Animals Inc.
- Age at study initiation: 16 weeks old.
- Weight at study initiation: 2.82 - 3.01kg
- Housing: Animals were individually housed in aluminium cages (W 360 x D 550 x H 350mm) with wire mesh bottoms.
- Diet (e.g. ad libitum): RC4 pelleted diet (Oriental Yeast Co., Ltd., Lot No's 111212 and 120113) ad libitum.
- Water (e.g. ad libitum): Tap Water ad libitum.
- Acclimation period: 21 days acclimation period for the animal in the 1st application and 23 days acclimation for the animals in the 2nd application.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 5°C (measured values 20 to 27°C)
- Humidity (%): 55 ± 25% (measured values 36 to 59%)
- Air changes (per hr): 11 - 14
- Photoperiod (hrs dark / hrs light): 12 hors light per day (07:00 - 19:00)

Vehicle:

unchanged (no vehicle)

Controls:

other: right eye of each test animal served as control.

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

For the 1st and 2nd step, a single application of the test material was applied to the conjunctival sac of the left eye.

Observation period (in vivo):

Observations were made at 1, 24, 48 and 72 hours after application.

Number of animals or in vitro replicates:

In the 1st step, one female test animal was used. In the 2nd step, 2 female test animals were used.

Details on study design:

REMOVAL OF TEST SUBSTANCE
Test material was not removed at completion of the exposure period.

SCORING SYSTEM:
The scoring system to assess ocular lesions was Draize Criteria (1959)
Eye irritation effects were evaluated according to the method of Kay and Calandra.

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-72h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: No effects observed

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: No effects observed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-72h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24h

Remarks on result:

other: Grade 1 effects were observed only at the one-hour observation and had resolved in all animals by 24 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-72h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: No effects observed

Irritant / corrosive response data:

No corrosive changes such as necrosis, ulcer or haemorrhage from 1 to 72 hours after application were observed in any animal. Conjunctival redness in animals and discharge in 1 animal were observed at 1 hours application (MTS: 2.7), however, these conjunctival changes had disappeared by 24 hours after application. No irritation reactions were observed in the cornea, iris or conjunctiva of any animal at either 24, 48 or 72 hours after application. In the corneal examination which was performed at 24hours after application, no fluoroscein stainnig marks were observed in any animal.
No abnormalities were observed in the control eye of any test animal.

Other effects:

No abnormal clinical signs were observed in any animal during the 72 hour observation period.
No abnormalities in body weight gain were observed in any animal during the observation period.

Observation		1h	24h	48h	72h	Mean (24-72h)
Cornea	Opacity	0.00	0.00	0.00	0.00	0.00
Iris	Lesion	0.00	0.00	0.00	0.00	0.00
Conjunctivae	Erythema	1.00	0.00	0.00	0.00	0.00
	Oedema	0.00	0.00	0.00	0.00	0.00

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was found to be a minimal eye irritant under the conditions of this study.

Executive summary:

In a study to determine the potential of aluminium titanium oxide to cause irritation or corrosion to the eyes of female Japanese white rabbits. The study was conducted according to GLP and OECD Guideline 405. Conjunctival redness was observed in all animals and discharge in one animal 1 hour after application, however, these conjuctival changes had disappeared 24 hours after application. There were no irritation reactions observed in the cornea, iris or conjunctiva of any animal at either 24, 48 or 72 hours after application.

The test material was found to be a minimal eye irritant under the conditions of this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study of skin irritation in the rabbit did not reveal any local effects in any animal at any timepoint. A study of eye irritation in the rabbit shows minimal transient conjunctival erythema.

Justification for selection of skin irritation / corrosion endpoint:
Only one study is available for this endpoint.

Justification for selection of eye irritation endpoint:
Only one study is available for this endpoint.

Justification for classification or non-classification

The results of the skin and eye irritation studies do not trigger classification for skin or eye irritation according to DSD or the CLP Regulation.