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Toxicological information

Skin irritation / corrosion

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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:
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:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification Bis (2-hydroxyethyl) hydrogenated tallow alkylamine (CAS Number 90367-28-5)
Description : pale brown solid block
Batch number : S-001017
Date received : 08 July 2009
Expiry date : 09 July 2017
Storage conditions: approximately 4°C in the dark under nitrogen

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
Erythema/Eschar Formation
Basis:
animal: 69116 male
Time point:
other: Mean score at 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible
Remarks:
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.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 & 72-hour mean score
Score:
2
Max. score:
2
Reversibility:
fully reversible
Remarks:
Fully reversible in 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.