Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-01-20 until 2003-01-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideine of 12 Nan No. 8147 as this is in line with QECD 404.

Principles of method if other than guideline:

None.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

443-860-6

EC Name:

-

Cas Number:

302776-68-7

Molecular formula:

C24 H31 N O4

IUPAC Name:

hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: About 9 months
- Sex: males and/or females
- Weight at study initiation: 3.95 - 3.98 kg
- Housing: Single housing in stainless steel wire mesh cages with grating (floor area 3000 cm2)
-The animals were housed in fully air-conditioned rooms, in which a central air-conditioning system ensured a temperature in the range of 20- 24°C and a relative humidity in the range of 30 - 70%.
- Diet: Kliba-Labordiät, Provimi Kuba SA, Kaiseraugst, Switzerland (about 130 g per animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

- Photoperiod (hrs dark / hrs light): 12 h light (6.00 a.m. - 6.00 p.m.)
12 h darkness (6.00 p.m. - 6.00 a.m.)

IN-LIFE DATES: From: 2003-01-20 To: 2003-01-27

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: One side of the back or flank of each animal was left untreated.

Amount / concentration applied:

TEST MATERIAL
The test patch (2.5 cm x 2.5 cm) was applied with an undiluted dose of 0.5 mL of the test substance (moistened with water, at about 60°C, but cooled down to body temperature before it was applied).

Duration of treatment / exposure:

4 hours.

Observation period:

7 days after removal of the patch

Number of animals:

3 rabbits.

Details on study design:

TEST SITE
The liquid test substance was applied undiluted in a single dose to the intact untreated skin through a patch. The test patch (2.5 cm x 2.5 cm) was applied to the flank of each animal and secured in position with a semiocclusive dressing. Because the test substance is applied undiluted or minimally moistened with doubly-distilled water, no analysis of the test substance in a vehicle was necessary.

REMOVAL OF TEST SUBSTANCE
The test substance was removed at the end of the exposure period with Lutrol and Lutrol / water (1:1).

SCORING SYSTEM: Evaluation of skin reactions (erythema and edema) is performed according to the quoted guidelines.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Remains of the TS still present after removal (4 hours).

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Remains of the TS still present after removal (4 hours). Pulling out of hair due to adhesive properties of the TS.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Remains of the TS still present after removal (4 hours).

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.3

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

No corrosive effects were observed.
Moderate/severe erythema (grade 2-3), observed 1 hour after removal of the patch in all animals, persisted up to 24 hours and decreased to slight erythema (grade 1) at the 48- and 72-hour reading. Moreover, remains of test substance was found on the skin of all animals during the observation period. In one animal mechanically pulled out hair due to adhesive test substance was recorded at the beginning of the study.
The cutaneous reactions were reversible in all animals within 7 days after removal of the patch.
Mean scores over 24, 48 and 72 hours for each animal and overall mean was 1.3 for erythema and 0.0 for edema

Other effects:

No other effects.

Any other information on results incl. tables

Readings	Animal	Exposure period: 4 h
		Erythema	Edema	Additional findings
1 h	01	2	0	RT
	02	2	0	RT, 26
	03	3	0	RT
24 h	01	2	0	RT
	02	2	0	RT, 26
	03	2	0	RT
48 h	01	1	0	RT
	02	1	0	RT
	03	1	0	RT
72 h	01	1	0
	02	1	0	RT
	03	1	0
7 d	01	0	0
	02	0	0	RT
	03	0	0
Mean	01	1.3	0.0
	02	1.3	0.0
	03	1.3	0.0
Mean	-	1.3	0.0

RT = Remains of test substance

26 = Mechanically pulled out hair due to adhesive test substance

Though results and evaluation indicate that the test substance has a slight irritation potential, it should be taken in account that the cutaneous reactions might be a secondary effect, related to a prolonged exposure period due to rests of test substance.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

According to the conditions of the test, the test substance has not to be classified as irritating to the skin following EU and the GHS requirements.