Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 10 June 2015 and 02 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

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
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
(3S,6E)-3,7,11-trimethyldodeca-6,10-dienal
EC Number:
810-298-1
Cas Number:
194934-66-2
Molecular formula:
C15H26O
IUPAC Name:
(3S,6E)-3,7,11-trimethyldodeca-6,10-dienal
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Two 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 2.19 or 2.64 kg and were 12 to 20 weeks old. After an acclimatization period of at least 5 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 12 hours continuous light (06:00 to 18:00) and 12 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:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL of neat test item
Duration of treatment / exposure:
4 hours
Observation period:
up to 14 days
Number of animals:
2
Details on study design:
On the day before the test two rabbits were 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. 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. 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 item 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 mL of test item. One patch was applied to the back of the rabbit and was allowed to remain in contact with the skin for a period of 4 hours.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
Erythema/Eschar Formation
Basis:
animal: 75097 Male
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
Erythema/Eschar Formation
Basis:
animal: 75124 male
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal: 75097 male
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal: 75124 male
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Skin Reactions
3-Minute Exposure Period
The individual scores for erythema/eschar and edema are given in Table 1.

Well defined erythema and very slight edema were noted at the treated skin site at the 24 and 48 Hour observations with very slight erythema and very slight edema at the 72 Hour observation. Moderate desquamation was noted at the treated skin site at the 7 Day observation.

The treated skin site appeared normal at the 14 Day observation.


1-Hour Exposure Period
The individual scores for erythema/eschar and edema are given in Table 1.

Well defined erythema and very slight edema were noted at the treated skin site at the 24 and 48 Hour observations with very slight erythema and very slight edema at the 72 Hour observation. Moderate desquamation 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 individual scores for erythema/eschar and edema are given in Table 2. The individual mean scores are given in Table 3.

Well defined erythema and very slight or slight edema were noted at one treated skin site with very slight erythema and slight edema noted at the other treated skin site immediately and 1 hour after treatment. Well defined erythema and very slight or slight edema were noted at both treated skin sites at the 24 and 48 Hour observations. Well defined erythema and very slight edema were noted at one treated skin site with very slight erythema noted at the other treated skin site at the 72 Hour observation. Slight desquamation was noted at one treated skin site at the 7 Day observation. Very slight erythema, very slight edema and moderate desquamation were noted at the other treated skin site at the 7 Day observation. This treated skin site appeared normal at the 14 Day observation.
Other effects:
Body Weight
Individual body weights and body weight change are given in Table 4.

Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Interpretation of Results Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

 

The scores for erythema and edema at the 24 and 72‑Hour readings were totaled for the two test rabbits (8 values) and this total was divided by 4 to give the primary irritation index of the test item. The test item was classified according to the following scheme devised by Draize, J.H. (1959):

 

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 item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

 

The results were also interpreted according to theGlobally Harmonized Systemof Classification and Labelling of Chemicals.

Table1     Individual Skin ReactionsFollowing 3-Minute and 1-Hour Exposures

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Rabbit Number and Sex

75097Male

3-Minute Exposure

1-Hour Exposure

Erythema/Eschar Formation

Immediately

0

0

1 Hour

0

0

24 Hours

2

2

48 Hours

2

2

72 Hours

1

1

7 Days

0D

0D

14 Days

0

0

Edema Formation

Immediately

0

0

1 Hour

0

0

24 Hours

1

1

48 Hours

1

1

72 Hours

1

1

7 Days

0

0

14 Days

0

0


D=   Moderate desquamation

Table2     Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Total

Rabbit Number and Sex

75097Male

75124Male

Erythema/Eschar Formation

Immediately

1

2

(3 )

1 Hour

1

2

( 3 )

24 Hours

2

2

4

48 Hours

2

2

( 4 )

72 Hours

2

1

3

7 Days

1D

0D*

( 1 )

14 Days

0

-

( 0 )

Edema Formation

Immediately

2

1

( 3 )

1 Hour

2

2

( 4 )

24 Hours

2

1

3

48 Hours

2

1

( 3 )

72 Hours

1

0

1

7 Days

1

0

( 1 )

14 Days

0

-

( 0 )

Sum of 24 and 72‑Hour Readings (S)           :          11

Primary Irritation Index (S/4)            :          11/4 = 2.8

Classification                                    :          MODERATEIRRITANT


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

D=          Moderate desquamation

D* =      Slight desquamation

- =          Not applicable

Table3     Individual and Mean Scores for Skin Reactions Following 4-Hour Exposure

Skin Reaction

Reading (Hours)

Individual Scores – Rabbit Number and Sex

75097Male

75124Male

Erythema/Eschar Formation

24

2

2

48

2

2

72

2

1

Total

6

5

Mean Score

2.0+

1.7+

Edema Formation

24

2

1

48

2

1

72

1

0

Total

5

2

Mean Score

1.7+

0.7


+=    Positive criterion according tothe Globally Harmonized System of Classification and Labelling of Chemicals

Table4     Individual Body Weights and Body Weight Change

Rabbit Number
and Sex

Individual Body Weight (kg)

Body Weight Change (kg)

75097
Male

Day 0

Day 14

0.26

2.64

2.90

75124
Male

Day 0

Day 7

0.18

2.19

2.37

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
The test item produced a primary irritation index of 2.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item was also classified as Category 3 (Mild irritant) according to the Globally Harmonized System of Classification and Labelling of Chemicals.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item following single, 3‑Minute, 1 and 4‑Hour, semi‑occluded applications to the intact rabbit skin.

 

 

Results

3‑Minute and 1‑Hour semi-occluded applications of the test item to the intact skin of one rabbit produced well-defined erythema, very slight edema and moderate desquamation. Both treated skin sites appeared normal at the 14‑Day observation.

 

A single 4‑Hour, semi occluded application of the test item to the intact skin of two rabbits produced well‑defined erythema and slight edema. Slight or moderate desquamation was noted at the treated skin sites at the 7‑Day observation. One treated skin site appeared normal at the 14‑Day observation. No corrosive effects were noted.

 

 

Conclusion

The test item produced a primary irritation index of 2.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

 

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

Categories Display