Reaction products of cyclohexylamine and 4-alkylaniline and 1,1'-methanediylbis(4-isocyanatobenzene)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1991-08-06 to 1991-08-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study in accordance with recognised test guideline but: Lot/batch No.: not stated Expiration date of the lot/batch: not stated NOTE: study deemed acceptable because spectral data for test item are available, covering approximately before and after the test period - see section 1.4 Analytical Information.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Di Urea Compound A-3622
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: Organic
- Physical state: Fine, of white powder
- Analytical purity: Approximately 100%
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: Not reported
- Purity test date: Not reported
- Lot/batch No.: Not reported
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported
- Storage condition of test material: ambient temperature
- Other: N/A

Specific details on test material used for the study:

- Substance type: Organic
- Physical state: Fine, off-white powder
- Analytical purity: Approximately 100%
- Storage condition of test material: ambient temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, England
- Age at study initiation: approximately three months
- Weight at study initiation: 2.52-2.82 kg
- Housing: They were individually housed in suspended stainless steel cages (Type RC10/L) mounted in mobile batteries (Modular Systems and Development Company Limited, London, England). The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly.
- Diet (e.g. ad libitum): free access to a commercially available standard pelleted rabbit diet (S.Q.C.Rabbit Diet, Special Diet Services Limited, Witham, Essex, England). The diet contained no added antibiotic or other chemotherapeutic or prophylactic treatment.
- Water (e.g. ad libitum): free access to tap water. The water was taken from the public supply; in England the supply and quality of this water is governed by Department of the Environment regulations. There was no information indicating that normal levels of common contaminants would influence the outcome of the study.
- Acclimation period: An acclimatisation period of seven days was allowed between arrival at the laboratory and administration of the test material.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (range 15°-23°C)
- Humidity (%): 55% R.H. (range 40%-70% R.H.)
- Air changes (per hr): 15 complete air changes per hour without re-circulation.
- Photoperiod (hrs dark / hrs light): lighting cycle of 12 hours of artificial light per day.

IN-LIFE DATES: From: 6 August 2009 To: 9 August 2009

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: the dorsum between the limb (6 x 6 cm) girdles
- Type of wrap if used: A single dose (0.5 g) was applied directly to the skin and covered by an unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of Blenderm (3-M Company). The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton wool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material during the four-hour exposure period. The elasticated bandage was held in place by thin strips of waterproof plaster ('Sleek' - T &J Smith and Nephew Limited) at both edges.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treatment sites were then gently washed with warm water and dried with paper towels to remove excess test material adhering to the skin.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
DRAIZE, JH (1959). In "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" p.47. Association of Food and Drug Officials of
the United States, Austin, Texas.

Actual criteria for assessment of skin irritation responses are given in Attached Background Information.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

No dermal response was observed at the test site of any animal at any time during the 72 hour observation period. The control sites did not show any response to the control procedure.

Any other information on results incl. tables

TABLE 1: Mean values for erythema and oedema 24, 48 and 72 hours after treatment

Animal number	Erythema		Oedema
	Test	Control	Test	Control
91 1435M 91 1438M 91 1442M	0.0 0.0 0.0	0.0 0.0 0.0	0.0 0.0 0.0	0.0 0.0 0.0

Scoring of irritance responses

Animal Number	Type of Response	Score after removal of dressings
		1 hour		24 hour		48 hour		72 hours
		Test site	Control site	Test site	Control site	Test site	Control site		Test site	Control site
91 1435M	Erythema	0	0	0	0	0	0		0	0
	Oedema	0	0	0	0	0	0		0	0
91 1438M	Erythema	0	0	0	0	0	0		0	0
	Oedema	0	0	0	0	0	0		0	0
91 1442M	Erythema	0	0	0	0	0	0		0	0
	Oedema	0	0	0	0	0	0		0	0

Applicant's summary and conclusion

Interpretation of results:

other: not irritanting

Conclusions:

Under the conditions of this test, the test item was classified as 'non-irritant' to the skin.

Executive summary:

The potential of test item to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 g of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours based on OECD 404.

Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings. No dermal response was observed at the test site of any animal at any time during the 72 hour observation period. Under the conditions of this test, the test item was classified as 'non-irritant' to the skin.