Lithium titanium oxide (Li4Ti5O12)

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

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

Test material

Test material information

Constituent 1

Reference substance name:

tetralithium(1+) 3,3-di{[oxido(oxo)titanio]oxy}-1,5-dioxotrititanoxane-1,5-bis(olate)

EC Number:

619-916-2

Cas Number:

12031-95-7

Molecular formula:

Li4Ti5O12

IUPAC Name:

tetralithium(1+) 3,3-di{[oxido(oxo)titanio]oxy}-1,5-dioxotrititanoxane-1,5-bis(olate)

Details on test material:

Name: Lithium-Titanium-Oxide
Synonym: Li4Ti5O12/T1
Batch number: 0857 VX 037
Appearance: White solid
Expiry date: 30 November 2012
Storage conditions: Room temperature

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 5.04 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.