Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 2016 (Protocol approved) - February 2017 (Final report signed)
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted on 17 December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Identity: TiH2
- Label name: Titanium Hydride Powder VM
- Batch no. :75727
- Expiry date: 21 June 2018
- Storage conditions: Room temperature
- RTC number: 15068

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS s.r.l., San Pietro al Natisone (UD), Italy
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6-7 weeks old
- Weight range at arrival: 148.4 - 184.3 grams and 157 -159 grams
- Fasting period before study: Food was removed from the cages overnight prior to dosing (Day -1) and was made available approximately 4 hours after dosing.
- Housing:Polisulphone solid bottomed cages measuring 59.5×38×20 cm with nesting material provided into suitable bedding bags
- Diet (e.g. ad libitum): 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy) - ad libitum throughout the study except for the dosing
- Water (e.g. ad libitum): Drinking water supplied to each cage via a water bottle - ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C±2 °C
- Humidity (%): 55%±15%
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: To: All animals were sacrificed on Day 15.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% aqueous solution of carboxymethylcellulose
Doses:
300, 2000 and 5000 mg/kg
No. of animals per sex per dose:
- Three females per group --> 4 groups: 300 mg/kg (2 times), 2000 mg/kg (2 times)
- 5000 mg/kg (1 female, one time) and (2 females for the second time)
Control animals:
no
Details on study design:
A first group of 3 female animals was dosed at a level of 300mg/kg (Step 1). Mortality did not occur. A second group, similarly composed, was then dosed at the same dose level (Step 2). No mortality occurred. A third group was dosed at 2000mg/kg. No death occurred. Therefore a fourth group was dosed at the same dose level. Since no nortality was seen, another female animal was dosed at 5000mg/kg and subsequently another two female animals were dosed
at the same dose level. Mortality did not occur. No further doses were investigated, since the objective of the study had been achieved.
Statistics:
No

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
other: Acute Toxicity expected (ATE)
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in any groups, at any dose level tested (300, 2000 and 5000mg/kg).
Clinical signs:
No clinical signs was observed in any groups, at any dose level tested (300, 2000 and 5000mg/kg).
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities were observed at necropsy examination performed on all animals dosed at 300, 2000 and 5000mg/kg, and in particular in the gastrointestinal
tract, at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
The acute toxicity of TiH2 was investigated following a single oral administration (10mL/kg in 1% carboxymethylcellulose) to the Sprague Dawley rat, followed by a 14-day observation period. No mortality occurred and no signs of toxicity were observed in all animals following dosing at 300, 2000 and 5000mg/kg.
These results indicate that the test item TiH2 did not induce toxic effects in the rat, following oral administration of a single dose at a level of 5000mg/kg. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 5000mg/kg body weight.
Executive summary:

The acute toxicity of TiH2 was investigated following a single oral administration to the Sprague Dawley rat, followed by a 14-day observation period.

- A first group of 3 female animals was initially dosed at 300mg/kg (Step 1). No mortality occurred and no clinical signs were observed.

- A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted.

- A third group of 3 female animals was dosed at 2000mg/kg (Step 3). No mortality occurred and no clinical signs were observed. Therefore another group of three females was dosed at the same dose level (Step 4). No death occurred and no clinical signs were noted.

- A single female animal was dosed at 5000mg/kg (Step 5). Since no mortality occurred, other 2 female animals were dosed at the same dose level. No death was seen and no clinical signs were noted.

Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination performed at the end of the observation period on animals of all groups. These results indicate that the test item TiH2 did not induce toxic effects in the rat, following oral administration of a single dose at a level of 5000mg/kg. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 5000mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC)No. 1272/2008 and subsequent revisions) would indicate the following:

- Classification: No category

- Signal word: No signal word required

- Hazard statement: No hazard statement required