Dineodymium tricarbonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 November 2009- 11 November 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

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

Details on test material:

- Name of test material (as cited in study report): dineodymium tricarbonate
- Substance type: extremely pale purple powder
- Physical state: solid
- Lot/batch No.: not provided, received 15 Feb 2010
- Expiration date of the lot/batch: 15 Jan 2011
- Storage condition of test material: room temperature in the dark over silica gel

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
- Fasting period before study:
- 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 analyzed
- 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

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

Range finding test: 25 uL 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 TESTS:
- Compound solubility: Compound was used as suspension in water
- Irritation: applied 3 consecutive days and observed up to day 6; any irritation was noted during this time
- Lymph node proliferation response: NDA

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA, 25%, 10% or 5% in propylene glycol applied on dorsal surface of ear 3 days in a row; [3H]-methyl thymidine was injected. All animals were observed daily, and weighed on day 1 and 6.
- Criteria used to consider a positive response: proliferation response was expressed as the number of radioactive disintegrations per mintue per lymph node and ratio of [3H]TdR incoproration relative to that recorded for control nodes was called the stimulation index. Material considered a sensitiser if ant least one cncentration resulted in a 3-fold greated incresase in radioactive incorporation compared tho the control values.

TREATMENT PREPARATION AND ADMINISTRATION: Test material was formulated withing 2 h of application; it was assumed that the formulation was stable; no analysis was conducted of compound, this is a deviation with regard to GLP.

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; it was considered to be a sensitiser

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Vehicle - na 5% - 1.1 10% 0.88 25% - 0.93

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Vehicle - 7529.69 dpm 5% - 8269.15 dpm 10% - 6613.97 dpm 25% 7025.55 dpm

Any other information on results incl. tables

No mortality or individual clinical observations

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

Table1            Clinical Observations, Bodyweight and Mortality Data – Preliminary Screening Test

Concentration (%w/w) in propylene glycol	Animal Number	Bodyweight (g)		Day
				1		2		3		4	5	6
		Day 1	Day 6	Pre-Dose	Post Dose	Pre-Dose	Post Dose	Pre-Dose	Post Dose
25	S-1	20	18	0	0	0	0	0	0	0	0	0

0=      No signs of systemic toxicity

Table2            Disintegrations per Minute, Disintegrations per Minute/Node and Stimulation Index

Concentration (%w/w) in propylene glycol	dpm	dpm/Node^a	Stimulation Index^b	Result
Vehicle	7529.69	941.21	na	na
5	8269.15	1033.64	1.10	Negative
10	6613.97	826.75	0.88	Negative
25	7025.55	878.19	0.93	Negative

 

dpm=  Disintegrations per minute

a=      Disintegrations per minute/node obtained by dividing the disintegrations per minute value by 8 (total number of lymph nodes)

b=      Stimulation Index of 3.0 or greater indicates a positive result

na =   Not applicable

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

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.