Reaction mass of 3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Taking effects as from 13th May 1998, until 29th January 2000

Test material

Test material information

Constituent 1

Reference substance name:

3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Cas Number:

173445-65-3

Molecular formula:

C14H18O

IUPAC Name:

3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Constituent 2

Reference substance name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Cas Number:

173445-44-8

Molecular formula:

C14H18O

IUPAC Name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): ST 22 C 99
- Physical state: colourless liquid
- Storage condition of test material: at room temperature, protected from light and under nitrogen gas

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: not reported
- Weight at study initiation: on the day of treatment, the animals had a mean body weight ± standard deviation of 2.5 ±0.3 kg.
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet (e.g. ad libitum): free access to 112 C pelleted diet (UAR, 91360 Villemoissonsur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external laboratories.
No contaminants were known to have been present in the diet or drinicing water at levels which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1999-10-06 To: 1999-10-13

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of one flank.

Duration of treatment / exposure:

4 hours

Observation period:

Examinations were done approximately 1 hour, 24, 48 and 72 hours after removal of the dressing, then daily up to reversibility (Day 8)

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: right flank
- Type of wrap if used: A single dose of 0.5 mL of the undiluted test substance was placed on a dry gauze pad, which was then applied to the right flank of the animals for 4 hours. The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not needed

SCORING SYSTEM:
Erythema and eschar formation:
0: - No erythema
1: - Very slight erythema (barely perceptible)
2: - Well defined erythema
3: - Moderate to severe erythema
4: - Severe erythema (beet redness) to slight eschar formation (injuries in depth)
Oedema formation:
0: - No oedema
1: - Very slight oedema (barely perceptible)
2: - Slight oedema (edges of area well defined by definite raising)
3: - Moderate oedema (raised approximately 1 mm)
4: - Severe oedema (raised more than 1 mm and extending beyond area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 120 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 96 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

A well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was observed on days 5, 6 and 7 in animal#1. See Table 7.3.1/1.

Other effects:

none

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

 

Score at time point / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	2 / 2 / 2	0 / 0 / 0
24 h	1 / 1 / 1	0 / 0 / 0
48 h	1 / 1 / 1	0 / 0 / 0
72 h	1 / 0 / 1	0 / 0 / 0
Average 24h, 48h, 72h	1.0 / 0.67 / 1.0	0.0 / 0.0 / 0.0
Reversibility*)	c.	-
Average time for reversion	120 hours	-

 

  *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material induces a slight to well-defined erythema being reversible within 6 days. Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test material was applied on the clipped skin of the right flank of 3 males New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 hours after the removal of the patch and up to reversibility.

A well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was recorded in one animal between day 5 and 7.

The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 1.00 / 0.67 / 1.00 for erythema and 0.00 / 0.00 / 0.00 for oedema.

Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.