Gallium

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17/07/2019 - 30/07/2019

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 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

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%

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

29 females
8-9 weeks, non-pregnant and nulliparous female animals were used. The health condition of animals was examined by a veterinarian
before initiation of the study. Animals were healthy, without visible signs of disease.

The animals were acclimated in identical conditions as during the experiment for 5 days prior to the start of treatment. The acclimation
was according to standard operation procedures.

The animals were housed in IVC polycarbonate cages (5 animals per cage) suspended on stainless steel racks, in a room equipped with
central air-conditioning. The room temperature was within the range of 22 ± 3 °C, relative humidity was at least of 30 % and did not exceed
70 %, the aim was 50-60 %. The light regime was set to a 12-hour light / 12-hour dark cycle. The sanitation was performed according to
standard operation procedures.

A laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was served ad libitum. The certificate of analysis is included in the raw data.

The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodically monitored (including microbiological control) and recorded; certificate of analysis is included in raw data.

Study design: in vivo (LLNA)

Vehicle:

dimethyl sulphoxide

Concentration:

25%, 50%, 100% w/v

No. of animals per dose:

5 per dose

Details on study design:

Five female mice (CBA/Ca) per group were topically exposed (dorsum of both ears) to the test item at concentrations of 25 %, 50 % and 100 % (corresponding to 1445, 2890 and 5780 mg/mL, respectively), to the positive control and to the vehicle only. Lymphocyte proliferation was measured using incorporation of radioactive 125I-iododeoxyuridine and 10-5M fluorodeoxyuridine in the draining lymph nodes. The radioactive incorporation was expressed as disintegrations per minute (DPM)/pooled treatment group and compared with DPM value from the vehicle control group and expressed as the Stimulation Index (SI).

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

SI = 4.51

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.23

Test group / Remarks:

25% Gallium(III) nitrate hydrate

Results 2

Parameter:

SI

Value:

1.11

Test group / Remarks:

50% Gallium(III) nitrate hydrate

Results 3

Parameter:

SI

Value:

1.66

Test group / Remarks:

100% Gallium(III) nitrate hydrate

Cellular proliferation data / Observations:

In comparison with the control group, no significant increase of the pooled lymph node weights was observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item Gallium (III) nitrate hydrate is not considered a skin sensitizer under the test conditions of this study (OECD 429).

Executive summary:

The sensitization of Gallium (III) nitrate hydrate was evaluated using the Local Lymph Node Assay (LLNA). The LLNA has been developed to determine the allergic contact sensitization potential of chemicals.

Based on the recommendations of the OECD 429, the test item was suspended in DMSO (w/v). The positive control (alpha-Hexylcinnamic aldehyde) (25 %) was dissolved in the same vehicle. The Pre-screen test was performed using the dose of 5780 mg test item/mL (referred to as 100 %). Based on the observations recorded in the Pre-screen tests, the concentration of 100 % was selected as top dose for the main test.

Five female mice (CBA/Ca) per group were topically exposed (dorsum of both ears) to the test itemat concentrations of 25 %, 50 % and 100 % (corresponding to 1445, 2890 and 5780 mg/mL, respectively), to the positive control and to the vehicle only. Lymphocyte proliferation was measured using incorporation of radioactive 125I-iododeoxyuridine and 10-5M fluorodeoxyuridine in the draining lymph nodes. The radioactive incorporation was expressed as disintegrations per minute

(DPM)/pooled treatment group and compared with DPM value from the vehicle control group and expressed as the Stimulation Index (SI).

After application of the test item at three concentrations (25 %, 50 % and 100 % w/v) the animals did not show visible clinical symptoms of either local irritation or systemic toxicity. In this study the Stimulation Indices (SI) of 1.23, 1.11 and 1.66 were determined with the test item at concentrations of 25 %, 50 %, and 100 % in DMSO, respectively. The EC3 value could not be

calculated, since none of the tested concentrations induced a SI greater than the threshold value of 3.

The test item Gallium (III) nitrate hydrate is not considered a skin sensitizer under the test conditions of this study.