Lithium titanium oxide (Li4Ti5O12)

Endpoint summary

Description of key information

Lithium titanium oxide is of low acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, CRl:CD(SD)
- Age at study initiation: ca. 8 weeks.
- Weight at study initiation: ca. 195 g
- Fasting period before study: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Housing: Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids.
- Diet (e.g. ad libitum): Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22.3 °C
- Humidity (%): average of 54.9 %
- Air changes (per hr): 12.
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: variable.
- Justification for choice of vehicle: The test substance was not soluble in water. Aqueous CMC is a common vehicle for acute oral toxicity testing.

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg.

DOSAGE PREPARATION: The suspensions were prepared freshly before administration and were administered within 15 minutes after the preparation.
Rationale for the selection of the starting dose: As no prior information on the toxicity of the test substance was available, a starting dose of 300 mg of the test substance per kg body weight was chosen.

Doses:

300 and 2000 mg/kg bw.

No. of animals per sex per dose:

2 steps à 3 rats = 6.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
- Body weights were determined before administration, 7 days p.a. and 14 days p.a.
- Necropsy of survivors performed: yes.

Statistics:

no.

Preliminary study:

n.a.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals did not show any clinical signs during the entire observation period.

Gross pathology:

No abnormal findings were made in all animals at the necropsy 14 d p.a.

Other findings:

none.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

An acute oral toxicity study according to the Acute Toxic Class method was performed with rats.

The LD50oral,14d is >2000 mg/kg bw.

No relevant signs of toxicity were observed up to 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline study with GLP.
The LD50 is >2000 mg/kg bw.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female CRL: (WI) Wistar strain rats were obtained from Charles River Laboratories, Research Models and Services (Germany GmbH, Sanhofer Weg 7, D-97633 Sulzfeld). After arrival, the animal’s health was certified by the resident veterinarian and after an acclimatisation period of 27 days, the animals were assigned to the study. The animals were randomised one day before the exposure. At randomisation, animals were young adult animals, 10 weeks old and in the weight range of 212 to 418 g (male 355 to 418g, female 212 to 251g) on day of exposure. The females were nulliparous and non-pregnant.

Husbandry:
The animals were housed in groups of five, by sex, in solid-floor cages (Type III) with stainless steel mesh lids and softwood flake bedding. The environmental controls were set to achieve target values of 22 ± 3 °C and 30-70 % relative humidity. The animal room was ventilated for at least 15 air exchanges per hour and the lighting controlled to give 12 hours of continuous artificial light in each twenty-four hour period.
Diet and Water:
The animals were provided with ssniff SM R/M-Z+H “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest Germany) and tap water for human consumption, ad libitum.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

The test item was used as supplied and no preparation was required.
Atmosphere Generation: The test item was aerosolised using a rotating brush powder disperser (Palas GmbH, Karlsruhe, Germany) located at the top of the exposure chamber and compressed air. The compressed air was passed through a respiratory quality filter train and condensate separator prior to use. The dust aerosol produced was then ducted to the exposure system using suitable tubing and various devices may have been included between the generation and exposure systems in order to increase the proportion of the aerosol in the target particle size range.
Animal Exposure System:
The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises of two, concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports. The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port. After passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic.
Exposure Procedure:
Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber. Only the nose of each animal was exposed to the test atmosphere. Following an equilibration period of at least the theoretical chamber equilibration time (T99), a group of ten rats (five male and five female) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 5 mg/L was used for the exposure. As no deaths occurred and the mean achieved concentration was 101 % of target, no further data were required.

Temperature in the chamber: mean = 24.8 (22.2 - 26.4)
Humidity in the chamber: mean =9.2 (7.0 - 15.0)
Oxygen: mean 0 20.0 (20.0 - 20.0)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Target concentration: 5 mg/L.
Nominal concentration: 11.32 mg/L
Actual mean concentration: 5.04 mg/L. SD: 0.21.

No. of animals per sex per dose:

5 males + 5 female rats.

Control animals:

no

Details on study design:

OBSERVATIONS
Morbidity/Mortality:
Animals were checked hourly during exposure, one hour after exposure and twice daily (early and late in the working day) during the 14-day observation period for morbidity and/or mortality.
Clinical Signs:
All animals were observed for clinical signs at hourly intervals during exposure, as soon as practically possible following removal from restraint at the end of exposure, one hour after exposure and subsequently once daily for fourteen days.
Bodyweight:
Individual bodyweights were recorded prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14.
Necropsy:
At the end of the fourteen day observation period, the animals were euthanised by exsanguination under anaesthesia and gross macroscopic examination was performed. All animals were subject to a gross necropsy which included a detailed examination of the abdominal and thoracic cavities. Special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity.

Statistics:

No.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: SD: 0.21

Mortality:

No deaths were observed.

Clinical signs:

other: Significant clinical signs commonly noted on the day of exposure included laboured respiration, respiratory rate increased and activity decreased. No abnormalities were detected in all animals from Day 1 until the end of the observation period.

Body weight:

Normal bodyweight gain was noted during the whole observation period for all animals.

Gross pathology:

No gross changes were detected.

The particle size distribution of the test atmosphere was as follows:

Mean Achieved (mg/L): 5.04

Mean Mass Median Aerodynamic Diameter (MMAD) (μm): 2.67

Geometric Standard Deviation: 1.92

Inhalable Fraction (% < 4μm): 73.2

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute inhalation median lethal concentration (4hr LC50) of Lithium-Titanium-Oxide, in rats, was greater than 5.04 mg/L.

Executive summary:

The study was performed to assess the acute inhalation toxicity of the test item. The methods used were OPPTS 870.1300, OECD 403 and EC 440/2008, B.2. A group of ten Wistar rats (five males and five females) was exposed to an dust atmosphere. The animals were exposed for 4 hours using a nose-only exposure system, followed by a fourteen day observation period.

Results:

The mean achieved atmosphere concentration:5.04 mg/L. SD = 0.21.

Mean Mass Median Aerodynamic Diameter (MMAD): 2.67 μm. SD = 1.92.

Inhalable Fraction (< 4μm): 73.2 %.

Mortality: no death occurred.

Clinical observations: Significant clinical signs commonly noted on the day of exposure included laboured respiration, respiratory rate increased and activity decreased. No abnormalities were detected in all animals from Day 1 until the end of the observation period.

Body weights: Normal bodyweight gain was noted during the whole observation period for all animals.

Necropsy: No gross changes were detected.

The acute inhalation median lethal concentration (4hr LC50) of Lithium-Titanium-Oxide, in rats, was greater than 5.04 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 040 mg/m³ air

Quality of whole database:

Guideline study with GLP.
The LC50 is >5040 mg/m³.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
The only study available. Guideline study with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The only study available. Guideline study with GLP.

Justification for classification or non-classification

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