Disodium hexatitanate

Endpoint summary

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:

05 October 2011 - 22 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline 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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

- Analytical purity: 100%
- Purity test date: 11 August 2011
- Lot/batch No.: IC96
- Expiration date of the lot/batch: 24 March 2014
- Storage: room temperature

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 209-235 g
- Housing: housed in groups of 3 rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid
- Diet (e.g. ad libitum): free access to a standard rodent diet (Rat and Mouse No.1 Maintenance Diet), except the overnight prior to and approximately 4 hours after dosing. The diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water (e.g. ad libitum): freely available via polycarbonate bottles fitted with sipper tubes
- Acclimation period: at least 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 -23 °C
- Humidity (%): 40 - 70%
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

DOSAGE PREPARATION: formulations were stirred before and after the dosing procedure.
- formulations were prepared on the day of dosing.

Doses:

The test substance was formulated at a concentration of 200 mg/ml in the vehicle and administered at a volume of 10 mL/kg bodyweight

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed soon after dosing and at frequent intervals for the remainder of Day1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of test substance was demonstrated to be greater than 2000 mg/kg bodyweight.

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:

13 August 2012 - 25 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: IC96
- Expiration date of the lot/batch: 24 March 2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at ambient temperature

Description: White powder
Purity: 100%

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
In the initial consignment of animals, 4 male and 4 female Crl:CD (SD) rats were received from Charles River (UK) Ltd. The rats were ordered at 56 to 84 days of age and within a weight range of ±20% of the mean bodyweight for each sex. The animals were allowed to acclimatise to the conditions described below for 6 days before treatment commenced. For those animals selected for this study, their age at the start of treatment was 62 to 90 days and their bodyweights were in the range of 330 to 351 g for males and 230 to 238 g for females.

Each animal room was supplied with filtered fresh air, which was passed to atmosphere and not re-circulated. The temperature and relative humidity controls were maintained within the range of 19 to 23°C and 40 to 70% respectively. Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

The animals were housed three of one sex per cage. The cages were made of a polycarbonate body with a stainless steel mesh lid. Wood shavings (Lignocel 3/4) were used as bedding and were sterilised by autoclaving and changed at appropriate intervals each week. Cages, food hoppers and water bottles were changed at appropriate intervals.

Whilst in the home cage, animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet). This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent. Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.7 µm

Geometric standard deviation (GSD):

2.6

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

No. of animals per sex per dose:

1 test group, which consisted of 3 male and 3 female animals

Control animals:

no

Sex:

male/female

Dose descriptor:

LC50

Effect level:

5.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no unscheduled deaths

Clinical signs:

other: The clinical sign of test substance staining to the snout and jaw was observed in 2/3 males and 2/3 females immediately after the exposure, this sign was no longer evident at 1 hour post dose. In addition wet fur was observed in all animals immediately af

Body weight:

There were slight bodyweight losses in the individual bodyweights of both sexes on the day following the exposure, recovery from any loss was observed at the next weighing occasion, Day 4, after which growth continued for the remainder of the study.

Gross pathology:

The macroscopic examination performed after a single administration followed by a 14-day observation period revealed enlargement and pallor to the tracheobronchial lymph node of a single female (Animal 6B). The nature and incidence of the other finding (pelvic dilatation of the right kidney of male 1B) were consistent with the commonly seen background of macroscopic changes.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this study the LC50 (4-hour) of Terracess DSR is in excess of 5.20 mg/L for male and female rats.
Terracess DSR is included in Category 5 or unclassified according to the Globally Harmonised System

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 November 2011 - 23 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Otsuka Chemical Co Ltd, batch IC96


- Storage condition of test material: Room temperature

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 373 to 401 g for males, and 242 to 255 for females


- Fasting period before study:
- Housing: individually from Day -1
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23C
- Humidity (%): 40 to 70%
- Air changes (per hr): periodic checks
- Photoperiod (hrs dark / hrs light): 12 hours

Type of coverage:

semiocclusive

Vehicle:

methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10
- Type of wrap if used: The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water (30 - 40°C)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Concentration (if solution): 2000 mg/kg bodyweight


VEHICLE
- Amount(s) applied (volume or weight with unit): 2.0 mL/kg bodyweight
- Concentration (if solution): 1%

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 morning only).

- Frequency of weighing: Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths and no clinical signs were observed for any animal.

Clinical signs:

other: Very slight erythema was seen in one female (Animal No. F7) from Day 4 resolving by Day 15. No dermal reactions were seen in the remaining animals throughout the study

Gross pathology:

Macroscopic examination at study termination on Day 15 revealed pallor of the kidneys in four males (Nos. F1 – F4) and three females (Nos. F6 – F8). No abnormalities were revealed in any other animal at the macroscopic examination at this time.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute median lethal dermal dose (LD50) to rats of Terracess DSR was demonstrated to be greater than 2000 mg/kg bodyweight.

Terracess DSR is included in Category 5 or unclassified according to the Globally Harmonised System