1,1'-(methylenedi-4,1-phenylene)bis(3-butylurea)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-07-09 to 1994-02-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC 92/69

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Version / remarks:

1990

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: M.A.F.F. no. 4200; 1985

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

416-600-4

EC Name:

-

Cas Number:

77703-56-1

Molecular formula:

C23H32N4O2

IUPAC Name:

3-butyl-1-[4-({4-[(butylcarbamoyl)amino]phenyl}methyl)phenyl]urea

Specific details on test material used for the study:

Analytical purity: >= 99.65 %
Lot/batch No.: 93.166;

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: E.S.D. (Romans, 01400, Chatillon-sur-Chalaronne, FRANCE);
- Age at study initiation: about 3 months;
- Weight at study initiation: 2.00 to 3.00 kg
- Housing: individually in stainless steel cages;
- Diet: 150 g/animal/day; pelleted complete rabbit diet (Diet reference 112 C - Usine d'Alimentation Rationnelle, Villemoisson, 91360 Epinay-sur-Orge, FRANCE);
- Water: softened and filtered mains drinking water, ad libitum;
- Acclimation period: at least 5 days;


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 +/- 3;
- Humidity (%): > 45 R.H. (target value);
- Air changes (per hr): minimum 12 air changes,;
- Photoperiod: 12 hours artificial light/12 hours dark;

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: sterile liquid paraffine acc. to Codex

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

6

Details on study design:

The test article was applied at the dose level of 0.5 g prepared as a paste with 0.32 g of sterile Codex liquid paraffin per animal, under a semi-occlusive bandage for 4 hours, to the intact skin of 6 New Zealand White male rabbits.
The cutaneous examinations were performed for erythema and oedema, according to a numerical scale, 1, 24 48 and 72 hours after removal of the bandage.
Besides, taking into account the lesions observed at 72 hours and in order to reveal a possible corrosive action of the test article, these readings were continued on Day 7.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

63724

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

63735

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

63737

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

63739

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

67340

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

63745

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.39

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

63724

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

63735

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

63737

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

63739

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

63740

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 13

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

63745

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Mean values for cutaneous irritation were as follows:
- erythema: 0.39;
- edema: 0.0;
The lesions observed at 72 hours showed a total reversibility at the reading performed on Day 7.
From the results obtained under the experimental conditions employed, application of this test article to the rabbit skin provoked a slight irritation. For further information, see Sect. "Remarks on results incl. tables and figures".

Other effects:

None

Any other information on results incl. tables

EVALUATION OF IRRITATION AFTER REMOVAL OF SEMI-OCCLUSIVE PATCHES

 

RABBITS N°		63724	63735	63737	63739	63740	63745	TOTAL	MEAN
ERYTHEMA	1 HOUR	1	1	0	1	1	1	5	0.83
	24 HOURS	1	0	1	1	1	0	4	0.67
	48 HOURS	1	0	0	1	0	0	2	0.33
	72 HOURS	0	0	0	1d	0	0	1	0.17
					ERYTHEMA: MEAN 24 H + 48 H + 72 H				0.39

 

RABBITS N°		63724	63735	63737	63739	63740	63745	TOTAL	MEAN
OEDEMA	1 HOUR	0	0	0	0	0	0	0	0.00
	24 HOURS	0	0	0	0	0	0	0	0.00
	48 HOURS	0	0	0	0	0	0	0	0.00
	72 HOURS	0	0	0	0	0	0	0	0.00
					OEDEMA: MEAN 24 H + 48 H + 72 H				0.00

 

OBSERVATIONS:

 

As an excess of test article was observed after removal of the semi-occlusive patch, a wiping was performed with a gauze pad moistened with purified water. The reading was carried out 1 hour later.

 

d: Slight desquamation of the epidermis to the application area.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

HAT ISO was tested in a skin irritation test in rabbits in a 4 h semi-occlusive application of the test material. After a 72 h observation period, slight irritation was observed with mean values of 0.39 for erythema and 0.0 for edema. The lesions observed showed a total reversibility at the reading performed on Day 7. No classification and labelling for skin irritation is necessary according to Regulation 1272/2008/EC (CLP).

Executive summary:

HAT ISO was tested in a skin irritation test in rabbits in a 4 h semi-occlusive application of the test material. After a 72 h observation period, slight irritation was observed with mean values of 0.39 for erythema and 0.0 for edema.

The lesions observed showed a total reversibility at the reading performed on Day 7. No classification as skin irritant is necessary.