Polyurea, produced by reacting aryl isocyanate with alkyl amines

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 15 November 2011 and 18 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

Sponsor's identification: Diurea thickener 8
Description : light brown solid
Batch number : not supplied
Purity : not supplied
Date received : 12 September 2011
Expiry date : not supplied
Storage conditions: room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.25 to 3.20 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930 Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: test material was moistened with 0.5 ml of distilled water.

Controls:

no

Amount / concentration applied:

0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water,

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 71324 male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal: 71325 Male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal: 71326 male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 4

Irritation parameter:

other: Oedema Formation

Basis:

animal: 71324 male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 5

Irritation parameter:

edema score

Basis:

animal: 71325 male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 6

Irritation parameter:

edema score

Basis:

animal: 71326 male

Time point:

other: Highest score at 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Irritant / corrosive response data:

The individual scores for erythema/eschar and oedema are given in Table 1.
No evidence of skin irritation was noted during the study.

Other effects:

Individual bodyweights and bodyweight changes are given in Table 2.
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Measurement of pH

The pH of the test item was determined prior to commencement of the study and found to be as follows:

Preparation	pH Measurement
	immediately	after 10 minutes
10% w/w aqueous preparation of the test item	9.1	9.1

Table 1              Individual Skin Reactions

Skin Reaction	Observation Time (following patch removal)	Individual Scores – Rabbit Number and Sex			Total
		71324Male	71325Male	71326Male
Erythema/Eschar Formation	Immediately	0	0	0	(0 )
	1 Hour	0	0	0	( 0 )
	24 Hours	0	0	0	0
	48 Hours	0	0	0	( 0 )
	72 Hours	0	0	0	0
Oedema Formation	Immediately	0	0	0	( 0 )
	1 Hour	0	0	0	( 0 )
	24 Hours	0	0	0	0
	48 Hours	0	0	0	( 0 )
	72 Hours	0	0	0	0
Sum of 24 and 72‑HourReadings(S)      :          0
Primary Irritation Index (S/6)                   :          0/6 = 0.0
Classification                                        :          NON‑IRRITANT

 

(   ) = Total values not used for calculation of primary irritation index

Table 2              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
71324Male	2.25	2.35	0.10
71325Male	2.33	2.44	0.11
71326Male	3.20	3.34	0.14

Interpretation of Results

Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the,,, p.47:

Primary Irritation Index	Classification of Irritancy
0	Non-irritant
> 0 to 2	Mild irritant
> 2 to 5	Moderate irritant
> 5 to 8	Severe irritant

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

The results were also evaluated according to the Classification, Labelling and Packaging Regulation and the Globally Harmonised System of Classification and Labelling of Chemicals.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize

Conclusions:

The test item produced a primary irritation index of 0.0 and was classified as non irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

Method B4 Acute Toxicity (Skin Irritation) of CommissionRegulation (EC) No. 440/2008

Results. A single 4‑Hour, semi-occluded application of the test item to the intact skin of three rabbits produced no evidence of skin irritation.

Conclusion. The test item produced a primary irritation index of 0.0 and was classified as non‑irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.