Dipotassium titanate(2-)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 January 2013 - 22 January 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147.

Version / remarks:

November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

dated 19/9/12

Test material

Test material information

Constituent 1

Reference substance name:

Dipotassium titanate(2-)

EC Number:

261-919-2

EC Name:

Dipotassium titanate(2-)

Cas Number:

59766-31-3

Molecular formula:

K2O17Ti8

IUPAC Name:

dipotassium titanate(2-)

Test material form:

solid: particulate/powder

Details on test material:

Appearance: White powder
Storage conditions: Room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Not indicated.
- Age at study initiation: Animals used within the study were 45 weeks old.
- Weight at study initiation: Body weights were 3.76 - 3.97 kg*.
- Housing: Individually housed in cages with perforated floors. Animals were given small soft white untreated wood blocks for environmental enrichment.
- Diet: 125 g of a standard laboratory rabbit diet per day. hay was offered during acclimatisation until two days prior to dose instillation, for the remainder of acclimatisation and throughout the study observation period wholemeal bread was offered.
- Water: Free access to tap water.
- Acclimation period: 21 to 31 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 – 20
- Humidity (%): 40 - 70
- Photoperiod (hrs dark / hrs light): 12/12

One day during the observation period a relative humidity of 32% was recorded; this had no impact on the health of the animals.

IN-LIFE DATES: From: 3 January 2013 to 22 January 2013

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL- Amount applied: approximately 55 mg (a volume of approximately 0.1 mL)

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance

Number of animals or in vitro replicates:

3 females

Details on study design:

TREATMENT
The dose was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped.
The eyelids were then gently held together for one second before releasing; the left eye remained untreated.

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

OBSERVATIONS (beschrijf beperkt)
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: \\tekst uit report overnemen.
- Necropsy: \\tekst uit report overnemen.
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.

An ophthalmoscope or pencil beam torch was available for use to facilitate inspection of the eyes.

Instillation of the test material gave rise to a moderate initial pain response in the sentinel animal; subsequent animals were pre-treated withy local anaesthesia.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #1

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #2

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

animal #3

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

Animal #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

Animal #1, #2 and #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animal #1 and #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Injection of the conjunctival blood vessels or a crimson-red conjunctival appearance was apparent in all animals throughout the first 48 hours after instillation. Very-slight to moderate chemosis was evident in all animals one hour after instillation, persisting to the 24 hour examination in two animals and to the 48 hour examination in the remaining animal. Moderate discharge was evident in one animal one hour after instillation. Scattered areas of opacity, covering up to a quarter of the corneal surface were apparent in two animals 24 hours after instillation and in one at the 48 hour examination.
The treated eye of all animals was overtly normal 72 hours after instillation.

Other effects:

There was no sign of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

according to Regulation (EC) 1272/2008

Conclusions:

In an eye irritation study with rabbits, performed according to OECD/EC test guidelines, limited irritation was observed which resolved within 72 hours in all animals. Based on these results TISMO-D is considered not irritating.

Executive summary:

An acute eye irritation study in the rabbit was performed with TISMO D according to OECD 405/EC guidelines and in accordance with GLP principles. Single samples of approximately 55 mg of test substane (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. Scattered areas of opacity, covering up to a quarter of the corneal surface were apparent in two animals 24 hours after instillation (score 1) and in one at the 48 hour examination (score 1). Very-slight to moderate chemosis was evident in all animals one hour after instillation, persisting to the 24 hours examination in two animals (score 1) and to the 48 hours examination in the remaining animal (score 2 at 24h and score 1 at 48 h). Moderate discharge was evident in one animal one hour after instillation. The irritation had resolved within 72 hours in all animals. Based on these results, TISMO D does not have to be classified and have no obligatory labelling requirement for eye irritation according to Regulation (EC) 1272/2008.