Ethanaminium, N-[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthalenyl]methylene]-2,5-cyclohexadien-1-ylidene]-N-ethyl-, molybdatetungstatephosphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 - 26 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have the same type of toxicological effects based on common underlying mechanisms (ECHA, 2015b). All substances have the same organic structural group (colorant) with different compositions of the inorganic group (metallic salt). Read-across is in this case based on the hypothesis that source and target substances have similar toxicological properties because they degrade to the similar chemical substances (ECHA, 2015c). This prediction is supported by physicochemical and toxicological data on the substances.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Name Target Substance Source Substance
Chemical name Ethanaminium, N-[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthalenyl]methylene]- Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+)
2,5-cyclohexadien-1-ylidene]-N-ethyl-, molybdatetungstatephosphate hexa(cyano-C)ferrate(4-)
IUPAC name Reaction product of [4-[bis[4-(diethylamino)phenyl]methylidene]naphthalen-1-ylidene]- Unknown
ethylazanium chloride with phosphotungstomolybdic acid
CAS No 1325-87-7 82338-76-9/57485-98-0
EC No 215-410-7 279-935-3
Colourant C.I. Basic Blue 7 (R30200) C.I. Basic Blue 7 (R30200)
Metals Phosphotungstomolybdic acid salt Copper ferrocyanide salt
Molecular weight range ≥ 6600 ≤ 10500 880-1750
Molecular formula (C33H40N3)z.O3.P2O5.(WO3)x.(MoO3)y C33H40N3.1/2C6FeN6.Cu
12 ≤ x+y ≤ 24 (x≥1; y≥1)
z = 6-10
Structural formula

Both substances are UVCB’s and so purity is considered to be 100%

3. ANALOGUE APPROACH JUSTIFICATION
The target substance CAS 1325-87-7is an organometallic multi-constituent substance. The source substance CAS 63022-06-0 has the same colourant (organic constituent) (see table above) as the target substance consisting of a basic [4-[bis[4-(diethylamino)phenyl]methylidene]naphthalen-1-ylidene]-ethylazanium. The inorganic Part B is different between source and target substances, consisting of the elements O, Mo, P and W for the target substance and Cu, Fe and CN for the source substance. These differences are expected to behave very similar. The target and source substances are thus considered suitable for the analogue approach based on structural similarity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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:

Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)

EC Number:

279-935-3

EC Name:

Bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)

Cas Number:

82338-76-9

Molecular formula:

C33H40N3.1/2C6FeN6.Cu

IUPAC Name:

bis[[4-[[4-(diethylamino)phenyl][4-(ethylamino)-1-naphthyl]methylene]cyclohexa-2,5-dien-1-ylidene]diethylammonium] dicopper(1+) hexa(cyano-C)ferrate(4-)

Test material form:

solid: nanoform

Remarks:

Purple powder

Details on test material:

specific surface area >100m2/cm3

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Batch no 278PE160900, Source Sponsor
- Expiration date of the lot/batch: 01 July 2022
- Purity test date: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Not performed


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
-The test substance was prepared as a suspension in propylene glycol. This vehicle was chosen as it produced the highest concentration that was suitable for dosing.

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Reputable commercial supplier
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known:
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15 - 23g
- Housing: solId floor propylene cages
- Diet (e.g. ad libitum): Teklad Global Rodent diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%)30 to 70%:
- Air changes (per hr): 1 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours darkness
- IN-LIFE DATES: From: To: 11-26 September 2017

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

2.5, 5 and 10% w/w

No. of animals per dose:

4

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility: not applicable
- Irritation:
- Systemic toxicity: None noted
- Ear thickness measurements: pre-dose on Day 1, post-dose on Day 3 and Day 6
- Erythema scores:

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
- Criteria used to consider a positive response:

TREATMENT PREPARATION AND ADMINISTRATION:

Statistics:

The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (disintegrations per minute/node) and as the ratio of3 HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in3 HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in3 HTdR incorporation will be classified as a "non-sensitizer".

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1.39

Test group / Remarks:

2.5% w/w

Results 2

Key result

Parameter:

SI

Value:

1.53

Test group / Remarks:

5% w/w

Results 3

Key result

Parameter:

SI

Value:

2.5

Test group / Remarks:

10% w/w

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA

DETAILS ON STIMULATION INDEX CALCULATION The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (disintegrations per minute/node) and as the ratio of3 HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

The test item will be regarded as a sensitizer if at least one concentration of the test item results in a threefold or greater increase in3 HTdR incorporation compared to control values. Any test item failing to produce a threefold or greater increase in3 HTdR incorporation will be classified as a "non-sensitizer".


EC3 CALCULATION

CLINICAL OBSERVATIONS: Purple staining of fur noted.
No signs of systemic toxicity were noted in the test or control animals during the test.

BODY WEIGHTS
Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

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