1-Octadecanamine, reaction products with 1,1'-methylenebis[4-isocyanatobenzene]

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 25 August 2009 and 05 September 2009.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

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. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2010

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

Reference substance name:

PU Thickener

IUPAC Name:

PU Thickener

Test material form:

other: beige solid pieces

Details on test material:

Sponsor's identification: PU Thickener
Description : beige coloured solid
Batch number : VPSG011
Date received : 31 July 2009
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:

Animals and Animal Husbandry
Two New Zealand White rabbits were supplied by (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK). At the start of the study the animals weighed 2.06 or 2.19 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 (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, 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:

water

Remarks:

test item was moistened with 0.5 ml of distilled water.

Controls:

no

Amount / concentration applied:

TEST ITEM
Amount(s) applied: 0.5 g

Concentration: Not applicable.

VEHICLE
Amount(s) applied: 0.5g of test material was moistened with 0.5 ml of distilled water.

Concentration: Not applicable.

Lot/batch no. : Not given in study report.

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

72 hours

Number of animals:

2

Details on study design:

Procedure
On the day before the test each rabbit 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.
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
After consideration of the skin reactions produced in the first animal, an additional animal was treated with 0.5 g of test material moistened with 0.5 ml of distilled water. One patch was applied to the back of the rabbit and was allowed to remain in contact with the skin for a period of four hours.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 68524 male

Time point:

other: 0, 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: 68543 Male

Time point:

other: 0, 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 3

Irritation parameter:

edema score

Basis:

animal: 68524 male

Time point:

other: 0, 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 4

Irritation parameter:

edema score

Basis:

animal: 68543 male

Time point:

other: 0, 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 remarks on results including tables and figures.
No evidence of skin irritation was noted during the study.

Any other information on results incl. tables

Table 1              Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction	Observation Time (following patch removal)	Individual Scores - Rabbit Number and Sex
		68524Male
		3-Minute Exposure	1-Hour Exposure
Erythema/Eschar Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0
Oedema Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0

Table 2              Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Scores – Rabbit Number and Sex		Total
		68524Male	68543Male
Erythema/Eschar Formation	Immediately	0	0	(0 )
	1 Hour	0	0	( 0 )
	24 Hours	0	0	0
	48 Hours	0	0	( 0 )
	72 Hours	0	0	0
Oedema Formation	Immediately	0	0	( 0 )
	1 Hour	0	0	( 0 )
	24 Hours	0	0	0
	48 Hours	0	0	( 0 )
	72 Hours	0	0	0
Sum of 24 and 72-hour Readings (S)       :          0
Primary Irritation Index (S/4)                   :          0/4 = 0.0
Classification                                        :          NON‑IRRITANT

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

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
68524Male	2.06	2.17	0.11
68543Male	2.19	2.24	0.05

 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 two test rabbits (8 values) and this total was divided by four 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 theUnited States,Austin,Texas, p.46‑59:

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.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

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

Conclusions:

The test material 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.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of 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. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit producedno evidence of skin irritation.

A single 4-hour, semi-occluded application of the test material to the intact skin of two rabbits produced no evidence of skin irritation.

Conclusion. The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme.