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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 August 2009-15 October 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:

other: Organisation for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Draft Proposal for a New Guideline: In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test Method.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: European Community (EC). Commission regulation (EC) No. 761/2009, Part B: Methods for the Determination of Toxicity and other health effects, Guideline B.46 “In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test ". Official Journal of the Eur

Deviations:

no

GLP compliance:

yes

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

Details on test material:

Test substance preparation
Skin tissue was moistened with 5 μl of Milli-Q water (Millipore Corp., Bedford, Mass., USA) to ensure close contact to the tissue and 10 mg of the solid test substance was applied directly on top of the skin tissue. WAY-173606 (crystallized) was spread to match the size of the tissue.

Reference substances
Negative control: Phosphate buffered saline (PBS, Invitrogen Corporation, Breda, The Netherlands).
Positive control: 5% (aq) Sodium dodecyl sulphate (SDS, Sigma Aldrich, Zwijndrecht, The Netherlands) [CAS Number 151-21-3].

Test animals

Species:

other: Not applicable

Strain:

other: Not applicable

Test system

Type of coverage:

other: Not applicable

Preparation of test site:

other: Not applicable

Vehicle:

water

Controls:

other: Not applicable

Duration of treatment / exposure:

15 minutes treatment and 42 hours of post incubation

Observation period:

Observations/measurements in the study were recorded electronically using the following programme(s):
REES Centron Environmental Monitoring system version SQL 2.0 (REES Scientific, Trenton, NJ, USA): Temperature and humidity.
Multiskan spectrum version 1.00 (Thermo labsystems, Breda, The Netherlands) for optical density measurement.

Number of animals:

three individual tissues

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

other: other: In vitro skin irritation test

Value:

> 50

Remarks on result:

other:

Remarks:

Basis: mean tissue viability. Time point: after 15 minutes treatment. Remarks: Since the mean relative tissue viability for WAY-173606 (crystallized) was above 50% WAY-173606 (crystallized) is considered to be non-irritant.. (migrated information)

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information in the in vitro skin irritation test Criteria used for interpretation of results: OECD GHS

Conclusions:

Finally, it is concluded that this test is valid and that WAY-173606 (crystallized) is non-irritant in the in vitro skin irritation test under the
experimental conditions described in this report.