p-tert-butylcinnamaldehyde

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available for the analogue substance 3-(4-tert-butylphenyl)propionaldehyde. The study was performed in line with good scientific principles in basic compliance with agreed protocols, with no or minor deviations from standard testing guidelines. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (3-(4-tert-butylphenyl)acrylaldehyde) and source substance (3-(4-tert-butylphenyl)propionaldehyde) and their similar physico-chemical properties.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

other: FDA Standards

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The test material was applied to both abraded and intact skin. A patch was not used to cover the test site to prevent ingestion. Removal of the test material was not reported, exposure was assumed to be 72 hours. Recovery of the animals was not evaluated.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3-(4-tert-butylphenyl)propionaldehyde

EC Number:

242-016-2

EC Name:

3-(4-tert-butylphenyl)propionaldehyde

Cas Number:

18127-01-0

IUPAC Name:

3-(4-tert-butylphenyl)propanal

Test material form:

other: liquid

Details on test material:

- Substance type: clear colourless liquid
- Physical state: Liquid
- Molecular formula (if other than submission substance): C13H18O
- Molecular weight (if other than submission substance): 190.2814
- Smiles notation (if other than submission substance): CC(C)(C)c1ccc(CCC=O)cc1
- InChl (if other than submission substance): InChI=1/C13H18O/c1-13(2,3)12-8-6-11(7-9-12)5-4-10-14/h6-10H,4-5H2,1-3H3
- Structural formula attached as image file (if other than submission substance): see Fig. 1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
New Zealand White rabbits were supplied by an accredited supplier.

- Age at study initiation:
Adult

- Weight at study initiation:
At the start of the study the animals were in the weight range of 2.5 - 3.0 kg

- Housing:
Not specified in the report

- Diet (e.g. ad libitum):
Not specified in the report

- Water (e.g. ad libitum):
Not specified in the report

- Acclimation period:
Not specified in the report

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
Not specified in the report

- Humidity (%):
Not specified in the report

- Air changes (per hr):
Not specified in the report

- Photoperiod (hrs dark / hrs light):
Not specified in the report

Test system

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Remarks:

undiluted test material

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
0.2 mL

- Concentration (if solution):
Not applicable.

VEHICLE
- Amount(s) applied (volume or weight with unit):
Not applicable

- Concentration (if solution):
Not applicable.

- Lot/batch no. (if required):
Notapplicable

Duration of treatment / exposure:

72 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure:
On the day of the test a suitable test site was selected on the back of each rabbit.

- % coverage:
Not given in study report.

- Type of wrap if used:
Test material was brought into contact with separated skin areas left of the midline of the back.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
Not reported

- Time after start of exposure:
72 hours.


SCORING SYSTEM:
The resulting skin reactions were evaluated by the method of Draize (J. Pharm. Exptl. Therap. 82 (1944) 377-390) 24, 48, 72 and 96 hours after application.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: erythema/edema

Basis:

animal: 8803

Time point:

other: Mean score at 24 and 72 hours

Score:

2

Max. score:

8

Reversibility:

no data

Results 2

Irritation parameter:

other: erythema/edema

Basis:

animal: 8804

Time point:

other: Mean at 24 and 72 hours

Score:

3

Max. score:

8

Reversibility:

no data

Results 3

Irritation parameter:

other: Erythema/edema

Basis:

animal: 8805

Time point:

other: mean at 24 and 72 hours

Score:

3

Max. score:

8

Reversibility:

no data

Results 4

Irritation parameter:

other: erythema/edema

Basis:

animal: 8806

Time point:

other: mean of 24 and 72 hours

Score:

2

Max. score:

8

Reversibility:

no data

Results 5

Irritation parameter:

other: erythema/edema

Basis:

animal: 8807

Time point:

other: mean at 24 and 72 hours

Score:

3

Max. score:

8

Reversibility:

no data

Results 6

Irritation parameter:

other: erythema/edema

Basis:

animal: 8808

Time point:

other: Mean at 24 and 72 hours

Score:

3

Max. score:

8

Reversibility:

no data

Irritant / corrosive response data:

Individual and average skin irritation scores are given in table 1. The test material caused severe skin irritation. Its dermal effects generally consisted of focal haemorrhages, slight to distinct ischemia and incrustation, and very slight edema.

ANALOGUE APPROACH JUSTIFICATION:
- See attached “Justification for read-across” document for full details.
- In summary, important considerations for the use of read-across for skin irritation are: i) 3-(4-tert-butylphenyl)acrylaldehyde (the target chemical) has similar predicted physico-chemical properties to those predicted and experimentally determined for 3-(4-tert-butylphenyl)propionaldehyde (the source substance), ii) there are structural similarities between the two chemicals and iii) the OECD QSAR Toolbox indicates that the two substances are expected to have similar interactions with biological receptors.
The information reported in this summary is included to demonstrate comparability between the source (3-(4-tert-butylphenyl)propionaldehyde) and target (3-(4-tert-butylphenyl)acrylaldehyde) substance.

Other effects:

None

Any other information on results incl. tables

TABLE 1 - INDIVIDUAL AND AVERAGE SKIN IRRITATION SCORES

Rabbit Number	Intact Skin		Rabbit Number	Abraded Skin
	24 hours	72 hours		24 hours	72 hours
	A                        B			A                        B
8803	4          -            1	2	8797	4          -            1	2
8804	4          -            1	3	8798	4          -            1	2
8805	4          -            1	3	8799	4          -            1	3
8806	4          -            1	2	8800	4          -            1	3
8807	4          -            1	3	8801	4          -            1	2
8808	4          -            1	3	8802	4          -            1	2
Average	5.0	2.7	Average	5.0	2.3

A = erythema

B = edema

The resulting skin reactions were evaluated by the method of Draize (J. Pharm. Exptl. Therap. 82 (1944) 377-390) 24, 48, 72 and 96 hours after application.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the present results it can be concluded that undiluted test material is a severe primary skin irritant.

Executive summary:

The test material was examined in primary skin irritation using New Zealand White albino rabbits as the experimental animals.

Pure and undiluted test material caused severe skin irritation.