2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Data is from BASF study reports

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

The objective was to assess the potential for skin irritation of the test material upon first contact with skin. The assessment of the skin irritation potential is included in international regulatory requirements for the testing of chemicals. Due to animal welfare reasons skin irritation was determined using the reconstructed human epidermal model EpiDermTM.The present test is based on the experience that irritant chemicals produce cytotoxicity in human reconstructed epidermis after a 1-hour topical exposure and about 42 hours postincubation.The test is designed to predict skin irritation potential of a chemical by using the three dimensional human epidermis model EpiDermTM. After application of the test material to the stratum corneum surface of the EpiDermTM tissue the induced cytotoxicity (=loss of viability) is measured by a colorimetric assay. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity. The mitochondrial dehydrogenase reduces the yellow colored water-soluble 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to the insoluble blue colored formazan. After isopropanol extraction of the formazan from the tissue the optical density of the extract is determined spectrophotometrically. Optical density of the extracts of test-item treated tissues is compared to negative control values from tissue treated with PBS and expressed as relative tissue viability.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone

EC Number:

219-210-0

EC Name:

2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone

Cas Number:

2387-03-3

Molecular formula:

C22H16N2O2

IUPAC Name:

1,1'-(hydrazine-1,2-diylidenedimethylylidene)di(2-naphthol)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report):Pigment Yellow 101 (Chemical Name: 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone)- Molecular formula (if other than submission substance):C22H16N202- Molecular weight (if other than submission substance):340,385g/mol- Smiles notation (if other than submission substance):Oc1c(c2c(cccc2)cc1)\C=N\N=C\c1c2c(cccc2)ccc1O- InChl (if other than submission substance):1S/C22H16N2O2/c25-21-11-9-15-5-1-3-7-17(15)19(21)13-23-24-14-20-18-8-4-2-6-16(18)10-12-22(20)26/h1-14,25-26H/b23-13+,24-14+- Substance type:Organic- Physical state:Solid- Lot/batch No.:29010809T0- Analytical purity:100%- Storage condition of test material:The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

Test animals

Species:

human

Strain:

other: not applicable

Test system

Type of coverage:

other: reconstructed three dimensional human epidermis model (EpiDerm™)

Preparation of test site:

other: incubation

Vehicle:

other: sterile PBS

Controls:

yes

Amount / concentration applied:

25 μL bulk volume (about 8 mg) CONTROLS:Negative control (NC): PBS, sterilePositive control (PC): 5% (w/v) sodium dodecyl sulfate (SDS, Sigma, Germany) in highly de-ionized water, sterile

Duration of treatment / exposure:

1 hour

Observation period:

42 hours

Number of animals:

Three dimensional human epidermis model

Details on study design:

EXPERIMENTAL PROCEDURE:Mesh compatibility:For liquid test items a nylon mesh can be used as a spreading support. However, this was not necessary for the solid test item.Thus no pretest for mesh compatibility was performed.Direct MTT reduction:To assess the ability of the test material to directly reduce MTT a pretest was performed as described below.Approximately 25 μL bulk volume of the test item was added to 0.9 mL of the MTT solution.The mixture was incubated in the dark at about 37 °C for 55 to 65 minutes. A negative control (50 μL of highly de-ionized water) was tested concurrently. If the MTT solution color or, in case of water-insoluble test items the border to the waterphase,turned blue / purple, the test item was presumed to directly reduce MTT.The direct reduction of MTT by a test item interferes with the color density produced by metabolic capacity of the tissue and would falsify the test results.In case that direct MTT reduction occurred and visible residues of the test item remained on the tissues after washing, subsequent testing of killed controls (one freeze-killed control tissue (KC)) was considered. Killed controls are treated with, each, the test article and the negative control, in the same way as described in section “Basic procedure” (3.6.3),additionally.

Results and discussion

In vivo

Results

Irritation parameter:

other: Mean tissue viability(% of negative control)

Basis:

mean

Time point:

other: 42 hrs.

Reversibility:

no data

Remarks on result:

other: > 50 % -non-irritant

Any other information on results incl. tables

FINDINGS:

Test article		tissue 1	tissue 2	tissue 3	mean	SD
NC	mean OD570	1.9402	1.8402	1.8907	1.8903
	viability [% of NC]	102.6	97.3	100.0	100	2.65
01/0031-2	mean OD570	2.0252	1.5387	1.6927	1.7522
	viability [% of NC]	107.1	81.4	89.5	93	13.15
PC	mean OD570	0.1067	0.1237	0.1212	0.1172
	viability [% of NC]	5.6	6.5	6.4	6	0.49

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Based on the observed results and applying the evaluation criteria it was concluded, that Pigment Yellow 101 (chemical name: 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone, CAS No 2387-03-3) does not show a skin irritation potential in the EpiDermTM skin irritation test under the test conditions chosen.

Executive summary:

The potential of Pigment Yellow 101 to cause dermal irritation was assessed by a single topical application of 25 μL bulk volume (about 8 mg) of the test item to a reconstructed three dimensional human epidermis model (EpiDerm™).

Three EpiDerm™ tissue samples were incubated with the test item for 1 hour followed by a 42-hours post-incubation period.

Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/ post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as suitable endpoint. The formazan production of the test item treated epidermal tissues is compared to that of negative control tissues. The quotient of both values indicates the relative tissue viability.

The EpiDerm skin irritation test showed the following results:

The test item is not able to reduce MTT directly.

The mean viability of the test-item treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 93%.

Based on the observed results it was concluded, that Pigment Yellow 101 does not show a skin irritation potential in the EpiDerm™ skin irritation test under the test conditions chosen.