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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 02 August 2011 and 09 August 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Esterification products of Fatty acids C18 unsaturated and triethanolamine
EC Number:
939-649-8
Cas Number:
1474044-69-3
Molecular formula:
Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)
IUPAC Name:
Esterification products of Fatty acids C18 unsaturated and triethanolamine
Test material form:
liquid: viscous

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.09 to 2.57 kg.
- Fasting period before study: None.
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2930 Teklad Global Certified Rabbit diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 17 to 23°C
- Humidity (%): Set to achieve limits of 30 to 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 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:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
A quantity of 0.5 ml of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch.
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
MEASUREMENT OF PH:
The pH of the test item was determined prior to commencement of the study and found to be as follows:
Undiluted as supplied: pH approximately 7.7 (immediately)
90% v/v aqueous preparation of the test item: pH 8.8 (immediately)
: pH 8.8 (after 10 minutes)

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.

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test item was applied directly to the skin 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.


SCORING SYSTEM:
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:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema.: 4

Oedema Formation
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

An additional observation was made on Day 7 to assess the reversibility of skin reactions.

Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 70793 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks:
7 days
Remarks on result:
other: Slight desquamation at 7 day observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 70794 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Slight desquamation at 7 day observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 70795 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 70793 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 70794 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 70795 - male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No effects at any observed time point
Irritant / corrosive response data:
The individual scores for erythema/eschar and oedema are given in Table 1.

Well-defined erythema and very slight oedema were noted at two treated skin sites with very slight erythema noted at one treated skin site at the 24, 48 and 72 Hour observations.

Slight desquamation was noted at two treated skin sites and the remaining treated skin site appeared normal at the 7 Day observation.
Other effects:
Bodyweight
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

The individual mean scores for erythema and oedema required for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals were as follows:

Skin Reaction

Reading (Hours)

Individual Scores – Rabbit Number and Sex

70793Male

70794Male

70795Male

Erythema/Eschar Formation

24

2

2

1

48

2

2

1

72

2

2

1

Total

6

6

3

Mean Score

2.0

2.0

1.0

Oedema Formation

24

1

1

0

48

1

1

0

72

1

1

0

Total

3

3

0

Mean Score

1.0

1.0

0.0

Table 1              Individual Skin Reactions

Skin Reaction

Observation Time
(following patch removal)

Individual Scores – Rabbit Number and Sex

Total

70793Male

70794Male

70795Male

Erythema/Eschar Formation

Immediately

0

0

0

(0 )

1 Hour

0

0

0

( 0 )

24 Hours

2

2

1

5

48 Hours

2

2

1

( 5 )

72 Hours

2

2

1

5

7 Days

0D

0D

0

( 0 )

Oedema Formation

Immediately

0

0

0

( 0 )

1 Hour

0

0

0

( 0 )

24 Hours

1

1

0

2

48 Hours

1

1

0

( 2 )

72 Hours

1

1

0

2

7 Days

0

0

0

( 0 )

Sum of 24 and 72-HourReadings(S)      :          14

Primary Irritation Index (S/6)                   :          14/6 = 2.3

Classification                                        :          MODERATE IRRITANT


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

D =     Slight desquamation

Table 2              Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 7

70793Male

2.09

2.23

0.14

70794Male

2.11

2.23

0.12

70795Male

2.57

2.73

0.16

Applicant's summary and conclusion

Interpretation of results:
other: Not classified as an irritant under CLP. Classified as an irritant under DSD.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 2.3 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item produced a maximum individual mean score of 2.0 and therefore did not meet the criteria for classification according to Regulation (EC) No. 1272/2008. The test item was classified as a Mild irritant (Category 3) according to the Globally Harmonised System of Classification and Labelling of Chemicals.
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 Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

Results. 

A single 4-Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight or well-defined erythema and very slight oedema. Slight desquamation was noted at two treated skin sites and the remaining treated skin site appeared normal at the 7-Day observation.

Conclusion. 

The test item produced a primary irritation index of 2.3 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item produced a maximum individual mean score of 2.0 and therefore did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP). 

The test item was classified as a Mild irritant (Category 3) according to the Globally Harmonised System of Classification and Labelling of Chemicals.

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