3-Quinolinecarbonitrile, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 July 2009 - 18 August 2009

Reliability:

1 (reliable without restriction)

Data source

Reference

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile

EC Number:

700-455-1

Cas Number:

380843-75-4

Molecular formula:

C26H29Cl2N5O3

IUPAC Name:

4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J strain, inbred, SPF-Quality.

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Remarks:

(Merck, Darmstadt, Germany).

Concentration:

10, 25 or 50% w/w on three consecutive days

No. of animals per dose:

10, 25 or 50% w/w on three consecutive days, by open application on the ears.
Five vehicle control animals were similarly treated, but with vehicle alone (Dimethyl formamide).
Three days after the last exposure, all animals were injected with H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

The SI values calculated for the substance concentrations 10, 25 and 50% were 3.9, 6.4 and 6.2 respectively. These results show that the test substance elicits an SI ≥ 3. The EC3 value (the estimated test substance concentration that will give a SI =3) was established to be between 0 and 10%.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean DPM/animal values for the experimental groups treated with test substance concentrations 10, 25 and 50% were 1029, 1684 and 1630 respectively. The mean DPM/animal value for the vehicle control group was 264.

Any other information on results incl. tables

Table 3: Radioactivity measurements (individual animals)

group                     test substance (1)(% w/w)                  animal                     DPM / animal

1                                          0%                                          1                            151

(Vehicle)                                       2                            342

3                            412

4                            227

5                            187

2                                          10%                                       6                            1421

7                              709

8                            145 (2)

9                              1217

10                              768

3                                          25%                                       11                             894

12                            2122

13                            1654

14                            2669

15                            1082

4                                          50%                                       16                            2075

17                            1904

18                            1278

19                            1306

20                            1586

(1). Vehicle: Dimethyl formamide

(2)Value rejected and not used for interpretation (animal showed abnormal small lymph nodes).

2. Value rejected and not used for interpretation (animal showed abnormal small lymph nodes).

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

Based on these results:
- according to the recommendations made in the test guidelines, WAY-173606 (CRYSTALLIZED) would be regarded as skin sensitizer.
- according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007), WAY-173606 (CRYSTALLIZED) should be classified as skin sensitizer (Category 1).
- according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, WAY-173606 (CRYSTALLIZED) should be classified as skin sensitizer (Category 1) and labeled as H317: May cause an allergic skin reaction.