Gallium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17/06/2019 - 11/07/2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Gallium trinitrate

Cas Number:

69365-72-6

Molecular formula:

Ga(NO3)3 x H2O

IUPAC Name:

Gallium trinitrate

Test material form:

solid

Specific details on test material used for the study:

Batch no MKCF5542
Ga content = 17.3%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

8-9 weeks; female animals were non-pregnant and nulliparous

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed, and the test item administered. After test item administration, food was withheld for further 3-4 hours.
The required amount of the test item (according to the body weight) was dissolved in vehicle (water for injection) shortly before administration. Dose was recalculated to concentration 100 % of Gallium (purity of test item was 17.3 %).

Doses:

2000 mg Ga/kg and 300 mg Ga/kg

No. of animals per sex per dose:

3 animals at 2000 mg Ga/kg and 6 at 300 mg Ga/kg

Control animals:

no

Details on study design:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. Available information indicated that the test item is likely to be non-toxic regarding acute toxicity. A limit dose of 2000 mg Ga/kg body weight was therefore used as a starting dose. In the first step, one group of 3 females was dosed. The test item in limit dose caused mortality of all three animals the first day after administration. In a second step, 3 females were treated at dose of 300 mg Ga/kg body weight. Test item-related mortality was not observed for 48 hours and therefore, in a third step, another 3 females were treated at the same dose level.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

element

Remarks:

Gallium

Mortality:

THe 3 females died at a dose of 2000 mg Ga/kg. Dose 300 mg/kg of body weight did not cause death in any animal.

Clinical signs:

other: The test item Gallium(III) nitrate hydrate administered to 3 females Wistar rats at a limit dose of 2000 mg Ga/kg caused immediate salivation and lethargy. Piloerection and sleep manifested starting ½ an hour after administration and persisted for 4 hours

Gross pathology:

All animals were necropsied. In animals No 1 and 2 dosed with 2000 mg Ga/kg body weight we observed necrosis of the stomach. No visible pathological findings were observed in animals dosed with 300 mg Ga/kg body weight.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test item Gallium(III) nitrate hydrate is greater than 300 mg Ga/kg and lower than 2000 mg Ga/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Gallium(III) nitrate hydrate is classified in GHS Category 4 with a LD50 cut off value 500 mg Ga/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “Gallium(III) nitrate hydrate” when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used.

A limit dose of 2000 mg Ga/kg body weight was used as a starting dose. Available information indicated that the test item is likely to be non-toxic regarding acute toxicity, therefore, a limit dose of 2000 mg Ga/kg body weight was used as a starting dose. In the first step, one group of 3 females was dosed. The test item in limit dose caused mortality of all animals the first day after administration. In a second step, 3 females were treated with dose of 300 mg Ga/kg body weight. The test item in dose 300 mg Ga/kg did not cause death in the next 48 hours and therefore another 3 females were treated at the same dose level.

The test item Gallium(III) nitrate hydrate administered to 3 females Wistar rats at a limit dose of 2000 mg Ga/kg caused immediate salivation and lethargy. Piloerection and sleep manifested starting ½ an hour after administration and persisted for 4 hours. The first day all three animals died. During necropsy we observed necrosis of the stomach in animal No 1 and 2.

Dose 300 mg/kg of body weight did not cause death in any animal nor evident signs of toxicity in animals No 4 and 5. Animal No 6 manifested immediate piloerection and lethargy. Animals No 7, 8, 9 were lethargic right after test item administration. Salivation occurred in animal No 7 immediately after test item administration. During necropsy, no macroscopic findings were observed.

The LD50 of the test item Gallium(III) nitrate hydrate is greater than 300 mg Ga/kg and lower than 2000 mg Ga/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Gallium(III) nitrate hydrate is classified in GHS Category 4 with a LD50 cut off value 500 mg Ga/kg body weight, after single oral administration to Wistar rats.