2,2'-(C16-18 (evennumbered) alkyl imino) diethanol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 April 2010 and 04 May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

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

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-(C16-18 (evennumbered) alkyl imino) diethanol

EC Number:

620-539-0

Cas Number:

1218787-30-4

Molecular formula:

No molecular formula

IUPAC Name:

2,2'-(C16-18 (evennumbered) alkyl imino) diethanol

Test material form:

other: liquid/paste

Details on test material:

- Chemical name: 2,2'-(C16-18 (evennumbered) alkyl imino) diethanol
- EC number: 620-539-0

To the best of knowledge, the sample used is representative to the boundary composition shared and agreed by each registrant.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMAL
- Source:
One New Zealand White rabbit supplied by an accredited supplier.

- Age at study initiation:
Twelve to twenty weeks old.

- Weight at study initiation:
At the start of the study the animal weighed 2.44 kg.

- Housing:
The animal wasindividually housed in a suspended cage.

- Diet (e.g. ad libitum):
Certified Rabbit Diet. ad libitum.

- Water (e.g. ad libitum):
ad libitum

- Acclimation period:
At least Five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
17 to 23°C

- Humidity (%):
30 to 70%
- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light):
The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Moistened sufficiently with 0.5 ml of distilled water

Controls:

no

Amount / concentration applied:

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

- Concentration (if solution):
Not applicable.

VEHICLE
Not applicable.

- Concentration (if solution):
Not applicable.

- Lot/batch no. (if required):
Not given in study report.

Duration of treatment / exposure:

3-minutes, 1-hour and 4 hours

Observation period:

14 days

Number of animals:

1

Details on study design:

TEST SITE
- Area of exposure:
On the day of the test a suitable test site was selected on the back of the rabbit.

- % coverage:
Not given in study report.

- Type of wrap if used:
Test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
Any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.

- Time after start of exposure:
3-minute, 1-hour and 4 hours.


SCORING SYSTEM:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale (table below).
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

Erythema/Eschar Formation

Basis:

animal: 69116 male

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Brown discolouration of the epidermis, loss of skin elasticty and loss of skin flexibility noted at the 24, 48 and 72-Hour observations. A hardened light brown coloured scab was noted at the 7-Day observation.

Results 2

Irritation parameter:

edema score

Basis:

animal: 69116 male

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

RESULTS

Skin Reactions

3-Minute Exposure Period

The scores for erythema/eschar and oedema are given in Table 1.
Very slight erythema was noted at the treated skin site at the 24, 48 and 72 Hour observations.
The treated skin site appeared normal at the 7-Day observation.

1-Hour Exposure Period

The scores for erythema/eschar and oedema are given in Table 1.
Well-defined erythema and very slight oedema were noted at the treated skin site at the 24, 48 and 72 Hour observations. Crust formation, preventing accurate evaluation of erythema and oedema, was noted at the treated skin site at the 7 Day observation.
The treated skin site appeared normal at the 14 Day observation.

4-Hour Exposure Period

The scores for erythema/eschar and oedema are given in Table 2.
Very slight erythema was noted at the treated skin site one hour after patch removal. Well-defined erythema, slight oedema, light brown discolouration and loss of skin elasticity and flexibility were noted at the treated skin site at the 24, 48 and 72-Hour observations. A hardened, light brown coloured scab, preventing accurate evaluation of erythema and oedema, was noted at the treated skin site at the 7 Day observation.
The treated skin site appeared normal at the 14 Day observation.

Any other information on results incl. tables

The individual scores for erythema/eschar and oedema are given in the folowing tables.

IndividualSkin Reactions - 3 -Minute and 1 -Hour exposures

Skin Reaction	Observation Time (following patch removal)	Individual Scores - Rabbit Number and Sex
		69116Male
		3-Minute Exposure	1-Hour Exposure
Erythema/Eschar Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	1	2
	48 Hours	1	2
	72 Hours	1	2
	7 Days	0	?eCf
	14 Days	0	0
Oedema Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	1
	48 Hours	0	1
	72 Hours	0	1
	7 Days	0	?od
	14 Days	0	0

Cf=     Crust formation

?e =    Adverse skin reactions prevent accurate evaluation of erythema

?od =  Adverse skin reactions prevent accurate evaluation of oedema

Table2              Skin ReactionsFollowing 4-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Scores – Rabbit Number and Sex
		69116Male
Erythema/Eschar Formation	Immediately	0
	1 Hour	1
	24 Hours	2BrLeLf
	48 Hours	2BrLeLf
	72 Hours	2BrLeLf
	7 Days	?eSp
	14 Days	0
Oedema Formation	Immediately	0
	1 Hour	0
	24 Hours	2
	48 Hours	2
	72 Hours	2
	7 Days	?od
	14 Days	0
Sum of 24 and 72-hour Readings (S)       :          8
Primary Irritation Index (S/2)                   :          8/2 = 4.0
Classification                                        :          MODERATE IRRITANT

Br=     Light brown discolouration of the epidermis

Le =    Loss of skin elasticity

Lf =     Loss of skin flexibility

Sp =   Hardened light dark brown coloured scab

?e =    Adverse skin reactions prevent accurate evaluation of erythema

?od =  Adverse skin reactions prevent accurate evaluation of oedema

The test material produced a primary irritation index of 4.0 and was classified as a MODERATE IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

 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.

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information EU - R38 "Irritating to skin". Criteria used for interpretation of results: other: EU and Draize

Conclusions:

The test material produced a primary irritation index of 4.0 and was classified as a MODERATE IRRITANT to rabbit skin according to the Draize classification scheme (based on one rabbit only). No corrosive effects were noted.
The test material produced positive criteria and was considered to be an irritant according to EU labelling regulations Commission Directive 2001/59/EC. The symbol “Xi”, the indication of danger “Irritant” and the risk phrase R 38 “IRRITATING TO SKIN” are therefore required. This corresponds to a CLP/GHS classification of Category 2 for skin irritation.

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 Commission Regulation (EC) No. 440/2008

Results. 

3-Minute and 1-Hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

A single 4-Hour, semi-occluded application of the test material to the intact skin of one rabbit produced well-defined erythema and slight oedema. Other skin reactions noted were light brown discolouration of the epidermis, loss of skin elasticity and flexibility and hardened, light brown coloured scab (preventing accurate evaluation of erythema and oedema). The treated skin site appeared normal at the 14‑Day observation.

Conclusion. 

The test material produced a primary irritation index of 4.0 and was classified as a MODERATE IRRITANT to rabbit skin according to the Draize classification scheme (based on one rabbit only). No corrosive effects were noted.

The test material produced positive criteria and was considered to be an irritant according to EU labelling regulations Commission Directive 2001/59/EC. The symbol “Xi”, the indication of danger “Irritant” and the risk phrase R 38 “IRRITATING TO SKIN” are therefore required.