potassium titanium oxide (K2Ti6O13)

Endpoint summary

Description of key information

The eye irritation potential of the test material was investigated in a in vivo test which was conducted under GLP conditions, according to Annex V.

The skin irritation potential of the test material was investigated in a in vivo test which was conducted under GLP conditions, according to Annex V.

The skin and eye irritancy of the test substance were tested in New Zealand White rabbits.

A single 4-hour, occluded application of the test material to the intact skin of six male rabbits produced no irritation responses observed on the normal skin except only slight erythema in 3/6 animals at 1 hour after tearing off the wraps, which recovered within 24 hours.

A single application of the test material to the non-irrigated eye of three rabbits produced minimal to moderate conjunctival irritation. All treated eyes appeared normal at the 72-hour observation. There was some evidence of the effects on the upper respiratory tract (nose), based on the local effects seen in the acute inhalation study (section 7.2.2 of the dossier).

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:

20 December 1989 to 31 January 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Male rabbits, from Japan SLC Co., Ltd., Koto-cho, Hamamatsu-shi, Shizuoka, Japan.
- Age at study initiation: Not reported.
- Weight at study initiation: 1.81 - 2.16 kg.
- Housing: Housed individually in a hanging stainless cage (35 X 50 X 35 cm: Toyo Riko k.k.)
- Diet (e.g. ad libitum): RC-4 (Oriental Yeast Industry k.k.), at libitum.
- Water (e.g. ad libitum): UV sterilised / filtred tap water, ad libitum.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2ºC.
- Humidity (%): 55 ± 10%.
- Air changes (per hr): 13 changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and 12 hours darkness.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: The test material as supplied was moistened with 0.5 ml of distilled water.

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 hours

Number of animals:

6 males.

Details on study design:

TEST SITE
- Area of exposure: 4 sites, area not specified, 1 inch square lint put on a moistureproof gum (approximately 4 X 4 cm)
- Type of wrap if used: elastic bandage and surgical tapes

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsed with slightly tepid water.
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
The test sites were examined for evidence of primary irritation and scored according to the grading in the test guideline. The results were interpreted under EU classification system.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 1 days

Other effects:

Slight erythema (score 1) was observed in 3 out of 6 animals at 1 hour only.
No significant changes in clinical signs were observed. No deaths occurred. There was no effects on body weight gain.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The primary skin irritation potential of potassium titanate of fibre was studied in rabbits according to the OECD Guidelines. The irritation response observed during the study period was only slight erythema (score 1) at 1 hour after tearing off the wraps and the reaction recovered (score 0) within 24 hours after tearing off the wraps. Therefore it was concluded that the skin irritation potential of the substance was quite minimal.
The test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008).

Executive summary:

To assess the skin irritation potential of potassium titanate fiber a primary skin irritation study was conducted in rabbits in accordance with the OECD guidelines.

During the study the skin of 6 New Zealand White rabbits was exposed to 500 mg of test material moistened with 0.5 mL of distilled water, under occlusion, for a period of 4 hours.

Slight erythema (score 1) was observed in 3 out of 6 animals; all changes were fully reversible within 1 day.

It was concluded that the skin irritation potential of potassium titanate fibre was quite minimum.

The test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008).

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:

13 July 1999 to 18 July 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(Annex V of Council Directive 67/548/EEC)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Date of inspection: 23 March 1998 Date of Signature: 21 July 1998)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, United Kingdom.
- Age at study initiation: 12 - 16 weeks old.
- Weight at study initiation: 2.43 - 2.63 kg.
- Housing: The animals were individually housed in suspended metal cages.
- Diet : STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, United Kingdom, ad libitum.
- Water : Mains water, ad libitum.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23°C.
- Humidity (%): 30 - 70%.
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eyes in the exposed animals were used for control.

Amount / concentration applied:

91 mg (equivalent to a volume of 0.1 ml)

Duration of treatment / exposure:

1, 24, 48 and 72 hours.

Observation period (in vivo):

(1, 24, 48 and 72 hours)

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No.


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the grading in the test guideline. The result was classified according to EU classification system.


TOOL USED TO ASSESS SCORE: The light source from a standard ophthalmoscope.


OTHERS
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular lesions were used. Initially, a single rabbit was treated. Immediately after administration of the test material, an assessment of the initial pain reaction was made. After consideration of the ocular responses produced in the first animal, two additional animals were treated.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(110 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: The highest score of 1 observed at 1 hour.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(143 Male)

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: The highest score of 2 was observed at 1 hour. Score of 1 was observed at 24 and 48 hour.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(144 Male)

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: The highest score of 2 was observed at 1 hour. Score of 1 was observed at 24 and 48 hour.

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(110 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

1

Remarks on result:

other: The highest score of 1 was observed at 1 hour.

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(143 Male)

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: The highest score of 1 was observed at 1 and 24 hour.

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(144 Male)

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: The highest score of 2 was observed at 1 hour. Score of 1 was observed at 24 hour.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(110 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(143 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(144 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(110 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(143 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(144 Male)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See table for the results. No corneal or iridial effects were noted during the study.

Minimal to moderate conjunctival irritation was noted in all treated eyes at the 1-hour observation. Minimal conjunctival irritation was noted in two treated eyes at the 24 and 48-hour observations.

Reversibility of any observed effect: Changes fully reversible within 3 days.

Other effects:

Not reported.


Minimal to moderate conjunctival irritation was noted in all
treated eyes at the 1-hour observation.

All eyes appeared normal at the 72-hour observation.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test material did not produce positive criteria in any rabbit therefore the test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008).

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

During the study 91 mg of test material was instilled in the eyes of 3 New Zealand White rabbits. Signs of ocular irritation were observed over a period of 72 hours.

A single application of the test material to the non-irrigated eye of three rabbits produced minimal to moderate conjunctival irritation. All treated eyes appeared normal at the 72-hour observation.

The test material does not meet the criteria for classification according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:  Study conclusion is the substance is not irritating.

The test material does not meet the criteria for classification of skin or eye irritation according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008 [CLP]).

The irritation/corrosion tests described above meet the requirements of OECD Test Guidelines and are assigned to be reliability score of 1 according to the scoring system of Klimisch et al (Klimisch et al., 1997).

This ranking was deemed appropriate because the studies were conducted the GLP certified laboratory and were in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

There are some evidence of the effects on the upper respiratory tract (nose), based on the local effects seen in the acute inhalation study (section 7.2.2 of the dossier).

Justification for classification or non-classification

Under the detailed test conditions, considering the experimental results, the test material was judged to be not irritating/not corrovise to the skin and to be not irritating/not corrovise to the eyes.

Skin corrosion/irritation

Slight erythema (score 1) was observed in 3 out of 6 animals; all changes were fully reversible within 1 day.

Eye damage/irritation

No corneal or iridial effects were noted during the study. Minimal to moderate conjunctival irritation was noted in all treated eyes at the 1-hour observation. All eyes appeared normal at the 72-hour observation.

Potassium titanium oxide is neither a skin nor eye irritant.

The test material does not meet the criteria for classification of skin or eye irritation according to EU classification system (Council Directive 67/548/EEC and Regulation (EC) No 1272/2008 [CLP]).