Lithium titanium oxide (Li4Ti5O12)

Endpoint summary

Description of key information

No relevant irritation was observed in an in vitro and an in vivo skin irritation test, and in an in vitro and in an in vivo eye irritation assay.

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:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, HUNGARY.
Age of animals at treatment: ~12 weeks old
Sex: Male
Body weight range at the beginning of the in-life phase: 2817 – 3161 g; at the end of the in-life phase: 2896 – 3195 g.
Acclimatization time: 14 days

Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature during the study: 17.1 – 19.8 °C
Relative humidity during the study: 37 – 85 %
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour

Animals received UNI diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary, ad libitum.
Water Supply: The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

0.5 g/site

Duration of treatment / exposure:

4 h.

Observation period:

3 days.

Number of animals:

3

Details on study design:

An initial test was performed using one animal. No severe irritation or corrosive effect was found in the initial test after 1 h exposure, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were then included in the study.
The test item was applied to an approximately 6 cm² area of intact skin.
After the treatment period, the test item was removed with water at body temperature.
Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48 and 72 hours after patch removal.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not relevant

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not relevant

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not relevant

Irritant / corrosive response data:

At observation 1, 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 at 72 hours after patch removal, the study was terminated after the 72 hours observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.00 respectively.
The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.00, 0.00 and 0.00 respectively.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

Other effects:

MORTALITY: There was no mortality observed during the study.
BODY WEIGHTS: There was no test item related effect on body weight.
General Daily Examination: There were no test item related clinical signs noted.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No irritation was observed on 3 rabbits after the dermal application of the test substance according to the OECD 404 method.

Executive summary:

An acute skin irritation study was performed with Lithium-Titanium-Oxide in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the method OECD 404 of 2002.

No skin irritation was observed in 3 rabbits after the dermal application of the test substance.

The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

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:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Source: S&K-LAP Kft.. 2173 Kartal, Császár út 135, Hungary
Animal health: Only animals in acceptable health condition were used for the test. Both eyes of each animal provisionally selected for testing were examined prior to starting the study. Animals showing eye irritation, ocular defects or pre-existing corneal injury were not used.
Age of animals at treatment: ~11 weeks old (adult)
Sex: Male
Body weight range at the beginning of the in-life phase: 2748 – 2799 g; end of the in-life phase: 2954 – 3027 g
Acclimatization time: 5 days

HUSBANDRY
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature during the study: 20 ± 3°C
Relative humidity during the study: 30 – 70 %
Housing/Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
Ventilation: 15-20 air exchanges/hour

FOOD AND FEEDING
Animals received UNI diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum. Contents of the diet are shown in Appendix 3.

WATER SUPPLY
The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g.

Duration of treatment / exposure:

The eyes of the test animals were washed out at 1 hour after application of test item.

Observation period (in vivo):

The eyes were examined at 1, 24, 48, 72 hours and 1 week after treatment.

Number of animals or in vitro replicates:

3 animals

Details on study design:

An initial test was performed using one animal. The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for a few seconds to prevent the loss of the test item. The contra lateral eye served as the control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first animal, one hour after the treatment of the first animal, two additional animals were treated.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n.a.

Irritation parameter:

other: discharge

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n.a.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 1 week

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 1 week

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 1 week

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n.a.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n.a.

Irritant / corrosive response data:

Initial Pain Reaction (IPR) (score 2) was observed in all animals.
One hour after the application, conjunctival redness (score 2) and discharge (score 2 or 1) were seen in all rabbits.
At 24 and 48 hours after treatment conjunctival redness (score 1 or 2) was seen in all rabbits.
At 72 hours after treatment, conjunctival redness (score 1) was seen in all rabbits.
At 1 week after treatment, no signs of eye irritation or other clinical signs were observed.
As all signs of eye irritation had fully reversed the study was terminated after a period of 1 week observation.

Other effects:

Mortality: There was no mortality observed during the study.
Body weights: The body weight and body weight change were considered to be normal with no indication of a treatment related effect.
General daily examination : There were no clinical signs observed that could be related to treatment.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Lithium-Titanium-Oxide does not require classification as an eye irritant.

Executive summary:

An acute eye irritation study with Lithium-Titanium-Oxide was performed in New Zealand White rabbits according to the OECD 405 method. Lithium-Titanium-Oxide, applied to rabbit eye mucosa, caused low grade conjunctival irritant effects at 1 to 72 h after application. The effects were fully reversible within 1 week.

According to the CLP-Regulation EC 1272/2008, Lithium-Titanium-Oxide does not require classification as an eye irritant.

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:
An in vivo guideline study with GLP.

Justification for selection of eye irritation endpoint:
An in vivo guideline study with GLP.

Justification for classification or non-classification

No indications were obtained to justify a classification of the substance.