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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:
The study was conducted between 20 May 2014 and 03 June 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is considered to be a reliability 1 as it has been conducted according to OECD Test Guideline 404 using the in vivo Acute Dermal Irritation/Corrosion method and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Identification: IFF TM 12-209
Storage Conditions: approximately 4 °C in the dark
Physical state / Appearance: extremely pale yellow liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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 2.92 to 3.10 kg and were twelve to twenty weeks old. After an acclimatization 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 (2930C Teklad Global 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. 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:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the test item was applied directly to the skin.

Test Item Formulation
For the purpose of the study the test item was used as supplied. The absorption of the test item was not determined.
Duration of treatment / exposure:
Four hours
Observation period:
14 days
Number of animals:
Three
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. A quantity of 0.5 mL of the undiluted 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.

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.

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

Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.

Individual body weights 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:
other: Erythema/Eschar Formation
Basis:
animal #1
Remarks:
74312 Male
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Erythema extended approximately 10 mm around the treated skin site. At the 7 day timepoint a score of 1 was given with slight desquamation noted.
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal #2
Remarks:
74313 Male
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Erythema extended approximately 10 mm around the treated skin site. At the 7 day timepoint a score of 1 was given with slight desquamation noted.
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal #3
Remarks:
74314 Male
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Erythema extended approximately 10 mm around the treated skin site. At the 7 day timepoint a score of 1 was given with slight desquamation noted.
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
74312 Male
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
74313 Male
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
74314 Male
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Well-defined erythema and very slight or slight edema were noted at all treated skin sites at the 24-Hour observation. Well defined erythema and very slight or slight edema were noted at two treated skin sites with very slight erythema and very slight edema noted at one treated skin site at the 48 Hour observation. Well defined erythema and very slight or slight edema were noted at all treated skin sites at the 72 Hour observation. The erythema extended approximately 10 mm around all treated skin sites at the 24 and 48 Hour observations. Very slight erythema and slight desquamation were noted at all treated skin sites at the 7 Day observation. All treated skin sites appeared normal at the 14 Day observation.
Other effects:
Body Weight
All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual Skin Reactions

Skin Reaction

Observation Time
(following patch removal)

Individual Scores – Rabbit Number and Sex

Total

74312 Male

74313 Male

74314 Male

Erythema/Eschar Formation

Immediately

0

0

0

(0 )

1 Hour

0

0

0

( 0 )

24 Hours

2R

2R

2R

6

48 Hours

2R

2R

1R

( 5 )

72 Hours

2

2

2

6

7 Days

1D

1D

1D

( 3 )

14 Days

0

0

0

( 0 )

Edema Formation

Immediately

0

0

0

( 0 )

1 Hour

0

0

0

( 0 )

24 Hours

2

1

1

4

48 Hours

2

1

1

( 4 )

72 Hours

2

1

1

4

7 Days

0

0

0

( 0 )

14 Days

0

0

0

( 0 )

Sum of 24 and 72-Hour Readings (S)           :          20

Primary Irritation Index (S/6)            :          20/6 = 3.3

Classification                                     :          MODERATE IRRITANT

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

R = Erythema extended approximately 10 mm around the treated skin site

D = Slight desquamation

Individual Body Weights and Body Weight Change

Rabbit Number
and Sex

Individual Body Weight (kg)

Body Weight Change (kg)

Day 0

Day 14

74312
Male

3.04

3.38

0.34

74313
Male

3.10

3.47

0.37

74314
Male

2.92

3.40

0.48

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 3.3 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item meets the criteria for classification as a Mild irritant (Category 3) according to the Globally Harmonized System of Classification and Labelling of Chemicals.

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

The dermal irritation potential of the test substance, TM 12-209, was assessed as not irritating according to OECD Test Guideline 404 using the in vivo Acute Dermal Irritation/Corrosion method.