Neodymium trihydroxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

5 November 2009 - 11 November 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (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:

Dineodymium tricarbonate

EC Number:

227-579-4

EC Name:

Dineodymium tricarbonate

Cas Number:

5895-46-5

Molecular formula:

CH2O3.2/3Nd

IUPAC Name:

dineodymium tricarbonate

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Dineodymium tricarbonate
- Substance type: Monoconstituent
- Physical state and appearance: Extremely pale purple powder
- Analytical purity: 99.7% as Nd2O3/TREO; 59.8% TREO
- Purity test date: 22 January 2010
- Storage condition of test material: At room temperature in the dark, or at room temperature in the dark over silica

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories, UK, Ltd, Oxon, UK
- Age at study initiation: nulliparous and non-pregnant
- Weight at study initiation: 15-23 g
- Housing: suspended solid floor polypropylene cages furnished with wood flakes
- Diet (e.g. ad libitum): ad libitum, 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon UK
- Water (e.g. ad libitum): ad libitum, free of contaminants as analysed
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 deg C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light and 12 h dark

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

Range finding test: 25 µL of test material at 25% w/w in propylene glycol
Main test: 5, 10 and 25% w/w in propylene glycol

No. of animals per dose:

4 females per dose

Details on study design:

RANGE FINDING TEST
- Compound solubility: Compound was used as suspension in water.
- Irritation: Applied for 3 consecutive days and observed up to day 6. Any irritation was noted during this time.
- Lymph node proliferation response: NDA

MAIN STUDY
TREATMENTS
- 25%, 10% or 5% test material in propylene glycol was applied on the dorsal surface of the ear for 3 days in a row. [3H]-methyl thymidine was injected. All animals were observed daily, and weighed on day 1 and 6.
- Test material was formulated within 2 h of application. It was assumed that the formulation was stable. No analysis was conducted of the compound, this is a deviation with regard to GLP.

CRITERIA USED TO CONSIDER A POSITIVE RESPONSE
Proliferation response was expressed as the number of radioactive disintegrations per minute per lymph node and the ratio of [3H]TdR incoproration relative to that recorded for control nodes (called the stimulation index). Material is considered as sensitising if at least one concentration resulted in a 3-fold greater increase in radioactive incorporation compared to the control values.

Positive control substance(s):

other: phenylacetaldehyde (90%)

Results and discussion

Positive control results:

2.5% phenylacetaldehyde in propylene glycol resulted in a stimulation index of 4.2, i.e. it was considered to be a sensitiser.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.1

Test group / Remarks:

5% w/w

Results 2

Parameter:

SI

Value:

0.88

Test group / Remarks:

10% w/w

Results 3

Parameter:

SI

Value:

0.93

Test group / Remarks:

25% w/w

Results 4

Parameter:

other: disintegrations per minute (DPM)

Value:

8 269.15

Test group / Remarks:

5% w/w

Results 5

Parameter:

other: disintegrations per minute (DPM)

Value:

6 613.97

Test group / Remarks:

10% w/w

Results 6

Parameter:

other: disintegrations per minute (DPM)

Value:

7 025.55

Test group / Remarks:

25% w/w

Results 7

Parameter:

other: disintegrations per minute (DPM)

Value:

7 529.69

Test group / Remarks:

vehicle

Cellular proliferation data / Observations:

No mortality or individual clinical observations

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was considered to be a non-sensitiser under the conditions of the test.

Executive summary:

A study was performed to assess the skin sensitisation potential of the test material in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. The method was designed to meet the requirements of the following: OECD Guideline for the Testing of Chemicals No. 429 "Skin Sensitisation: Local Lymph Node Assay" (adopted 24 April 2002) and Method B42 Skin Sensitisation (Local Lymph Node Assay) of Commission Regulation (EC) No. 440/2008.

Following a preliminary screening test in which no clinical signs of toxicity were noted at a maximum attainable concentration of 25% w/w, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of four animals, were treated with 50 µl (25 µl per ear) of the test material as a suspension in propylene glycol at concentrations of 25%, 10% or 5% w/w. A further group of four animals was treated with propylene glycol alone.

The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:

Concentration (%w/w) in propylene glycol	Stimulation Index	Result
5	1.10	Negative
10	0.88	Negative
25	0.93	Negative

The test material was considered to be a non-sensitiser under the conditions of the test.